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Instructions for Acute Myelogenous Leukemia Pre-HCT Data
(Form 2010 – Revision 3)
This section of the CIBMTR Forms Instruction Manual is intended to be a
resource for completing the AML Pre-HCT Form.
E-mail comments regarding the content of the CIBMTR Forms Instruction Manual
to: [email protected]. Comments will be considered
for future manual updates and revisions. For questions that require an immediate
response, please contact your transplant center’s CIBMTR CRC.
TABLE OF CONTENTS
Key Fields ............................................................................................................. 2
Subsequent Transplant ......................................................................................... 2
Disease Assessment at Diagnosis ........................................................................ 3
Laboratory Studies at Diagnosis ......................................................................... 12
Pre-HCT Therapy................................................................................................ 18
Laboratory Studies at Last Evaluation Prior to the Start of the Preparative
Regimen ........................................................................................................ 23
Disease Status at Last Evaluation Prior to the Start of the Preparative Regimen
...................................................................................................................... 27
Manual Change History ...................................................................................... 31
Acute Myelogenous Leukemia (AML) Pre-HCT Data
Acute Myelogenous Leukemia (AML) is a cancer of the white blood cells. It is
characterized by the rapid proliferation of abnormal, immature myelocytes,
known as myeloblasts, in the bone marrow. This accumulation of blasts in the
marrow prevents the formation of healthy red blood cells, white blood cells,
and/or platelets. Normal myeloblasts develop into neutrophils, basophils, and
eosinophils, which are all white blood cells that fight infection. In AML, the
leukemic myeloblasts do not fully develop and are unable to fight infection. The
symptoms of AML result from a drop in red blood cell, platelet, and normal white
blood cell counts caused by the replacement of normal bone marrow with
leukemic cells.
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Certain prognostic indicators are associated with poorer outcomes. These
include advanced age (50+ years of age), AML arising from MDS or
secondary/therapy-related AML, and certain genetic mutations that are described
in greater detail later in this manual.
The Acute Myelogenous Leukemia Pre-HCT Data Form is one of the
Comprehensive Report Forms. This form captures AML-specific pre-HCT data
such as: the recipient’s hematologic and cytogenetic findings at the time of
diagnosis and prior to the start of the preparative regimen, pre-HCT treatments
administered, and disease status prior to the preparative regimen.
This form must be completed for all recipients randomized to the Comprehensive
Report Form (CRF) track whose primary disease is reported on Form 2400,
question 357, as Acute Myelogenous Leukemia (AML or ANLL). Additional
disease insert forms will be required if the recipient had
Myelodysplastic/Myeloproliferative Syndrome (MDS/MPS), Aplastic Anemia, or
Juvenile Myelomonocytic Leukemia (JMML) prior to their diagnosis of Acute
Myelogenous Leukemia.
Key Fields
Accuracy of the Key Fields is essential for ensuring that:
Data are being reported for the correct recipient.
Outcomes data accurately reflects appropriate transplant type and product
for each transplant center.
Data are being shared with the correct donor center, cord blood bank,
cooperative registry, or other agency.
The Key Fields precede the form body and are automatically populated in the
FormsNet3SM application based on information provided on the CRID
Assignment Form 2804. If errors are noted in the key fields, correct Form 2804
and then review it for accuracy. After Form 2804 has been corrected, verify data
has been updated on all completed forms. If the data has not been updated
automatically, centers will need to reprocess the completed forms to correct the
key field data. If errors are noted in key fields for second or subsequent
transplants, contact your CRC to make any necessary corrections to the
transplant or product type. Transplant and product type will not be automatically
populated on product or donor specific forms (Forms 2004, 2005, and 2006) and
will need to be manually reported.
Subsequent Transplant
If this is a report of a second or subsequent transplant for the same disease
subtype and this baseline disease insert was not completed for the previous
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
transplant (e.g., patient was on TED track for the prior HCT, prior HCT was
autologous with no consent, etc.), begin at question 1.
If this is a report of a second or subsequent transplant for a different disease
(e.g., patient was previously transplanted for a disease other than Acute
Myelogenous Leukemia), begin at question 1.
If this is a report of a second or subsequent transplant for the same disease and
this baseline AML disease insert has previously been completed, check the
indicator box and continue with question 127.
Disease Assessment at Diagnosis
Question 1: What was the date of diagnosis?
Report the date of the first pathological diagnosis (e.g., bone marrow biopsy,
extramedullary mass biopsy) of AML. Enter the date the sample was collected for
examination. If the diagnosis was determined at an outside center and no
documentation of a pathological or laboratory assessment is available, the
dictated date of diagnosis within a physician note may be reported. Do not report
the date symptoms first appeared. The date of diagnosis is important because
the interval between diagnosis and HCT is often a significant indicator for the
recipient’s prognosis post-HCT.
If the exact pathological diagnosis date is not known, use the process for
reporting partial or unknown dates as described in General Instructions,
Guidelines for Completing Forms.
Question 2: Is the disease (AML) therapy-related? (not MDS/MPN)
Agents such as radiation or systemic therapy used to treat other diseases (e.g.,
Hodgkin lymphoma, non-Hodgkin lymphoma, and breast cancer) can damage
the marrow and lead to a secondary malignancy such as AML. If the diagnosis of
AML is therapy-related, check “yes” and continue with question 3.
If the diagnosis of AML is not therapy-related, check “no” and continue with
question 11.
If AML was preceded by therapy-related MDS, check “no.”
If the recipient developed AML after an environmental exposure (e.g.,
exposure to benzene), check “no.”
If it is unknown whether or not the diagnosis of AML was therapy-related, check
“unknown” and continue with question 11.
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
Page 3 of 31
Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Questions 3-4: Specify prior disease.
Indicate the recipient’s primary disease before the diagnosis of therapy-related
AML. If the patient’s prior disease is best classified as “other disease (malignant
or non-malignant),” specify in question 4.
Questions 5-6: Date of diagnosis of prior disease.
Specify if the date of diagnosis of the prior disease is “known” or “unknown.” If
the date is “known,” continue with question 6 and report the date of the first
pathological diagnosis (e.g., bone marrow or tissue biopsy) of the prior disease.
Enter the date the sample was collected for examination. Do not report the date
symptoms first appeared. This date must be prior to the AML diagnosis date
entered in question 1.
If the date is “unknown,” continue with question 7.
Questions 7-10: Specify therapy for prior disease.
Systemic therapy refers to a delivery mechanism where a therapeutic agent is
delivered orally or intravenously, enters the bloodstream, and is distributed
throughout the body. Systemic therapy in the setting of malignancy generally
refers to chemotherapy or cytotoxic therapy. Intrathecal therapy is administered
into the lumbar cerebral spinal fluid and acts on the central nervous system.
Radiation therapy uses high-energy, ionizing radiation to kill malignant cells. It is
typically referred to as radiation therapy, x-ray therapy (XRT), or radiotherapy.
For each listed treatment, indicate “yes,” “no,” or “unknown.” If the treatment
administered was “other treatment,” specify the type of treatment given in
question 10. Check all that apply; do not leave any response blank.
Question 11: Did the recipient have an antecedent hematologic disorder
(preleukemia or myelodysplastic syndrome)?
AML may evolve from MDS or MPS. This transformation is typically distinguished
by the percentage of blasts in the bone marrow. AML that transforms from MDS
or MPS has a poorer survival prognosis because of the association with
unfavorable chromosomal abnormalities.
AML can also evolve from Juvenile Myelomonocytic Leukemia (JMML). JMML is
a rare form of chronic leukemia that affects young children, usually before the
age of five. JMML results from DNA mutations in white blood cells called
monocytes. Normal monocytes attack invading microorganisms and assist
lymphocytes in carrying out immune functions. Abnormal monocytes in JMML
accumulate in the bone marrow and interfere with the production of normal white
blood cells, red blood cells, and platelets.
Additionally, aplastic anemia may progress to MDS and/or AML. Aplastic anemia
is a broad classification that refers to bone marrow failure characterized by
pancytopenia and marrow hypoplasia.
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
If there is documentation of a diagnosed or suspected antecedent (prior)
hematologic disorder or a concurrently diagnosed hematologic disorder, check
“yes” and continue with question 12.
If the recipient did not have a documented or suspected antecedent hematologic
disorder or concurrent diagnosis of another hematologic disorder, check “no” and
continue with question 16.
If it is unknown whether the recipient had a documented or suspected antecedent
hematologic disorder, check “unknown” and continue with question 16.
Question 12: Specify if the antecedent hematologic disorder was:
If the patient’s other hematologic disorder diagnosis preceded their AML
diagnosis indicate “documented” and continue with question 13.
If the other hematologic disorder was diagnosed on the same evaluation that
resulted in AML diagnosis, indicate “concurrent” diagnosis and continue with
question 13.
If the patient is suspected to have had a preceding hematologic disorder, but it
was not definitively documented or diagnosed, indicate “suspected” and continue
with question 14.
Question 13: What was the date of diagnosis of antecedent hematologic
disorder?
Report the date of the first pathological diagnosis (e.g., bone marrow or tissue
biopsy) of the antecedent hematologic disorder. Enter the date the sample was
collected for examination. Do not report the date symptoms first appeared. This
date must be prior to the AML diagnosis date entered in question 1 for
documented antecedent hematologic disorders; however, this date should be the
same as the AML diagnosis date entered in question 1 for concurrently
diagnosed hematologic disorders.
EXAMPLE 1: Patient presents with fatigue; initial work-up reveals anemia.
Subsequent bone marrow biopsy with specimen taken on May 14 shows
MDS, refractory anemia with excess blasts at 7%, or RAEB-1. The patient
chooses supportive therapy and their disease progresses to AML, which is
shown in a bone marrow biopsy with 28% blasts on September 7 of the
same year. This patient had a known antecedent hematologic disorder.
May 14 would be reported as the date of diagnosis of antecedent
hematologic disorder, which was RAEB-1 (reported in question 13). The
diagnosis date of AML (question 1) would be reported as September 7.
EXAMPLE 2: Patient presents with severe fatigue and chronic upper
respiratory infections; initial work-up reveals anemia. Subsequent bone
marrow biopsy with specimen taken June 17 shows 26% blasts and
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
myelodysplasia-related features; an aspirate sample was sent for
cytogenetic testing, which reveals monosomy 7. The physician states that
this patient has AML arising from MDS. Report that the patient had a
concurrent hematologic disorder. June 17 would be reported as the date
of antecedent hematologic disorder (question 13) and the diagnosis date
of AML (question 1).
Question 14-15: What was the classification of the hematologic disorder at
diagnosis?
Indicate the classification of the antecedent hematologic disorder at diagnosis.
Do not report any transformations or progressions of an antecedent hematologic
disorder. For example: a patient is diagnosed with RAEB-1, which progresses to
RAEB-2 prior to transformation to AML; report “RAEB-1” as the antecedent
hematologic disorder.
Report myelodysplastic syndrome that has not been classified as
“Myelodysplastic syndrome, unclassifiable.”
Table 1. Hematologic disorders and characteristics
DISEASE
DIAGNOSTIC CHARACTERISTICS
Refractory Cytopenia with Unilineage
Dysplasia (RCUD)
If selected, continue with question 16. Also
complete CIBMTR Form 2014.
Refractory Anemia with Ringed
Sideroblasts (RARS)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Refractory Anemia with Excess Blasts
(RAEB-1)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Includes Refractory Anemia (RA),
Refractory Neutropenia (RN), and
Refractory Thrombocytopenia (RT)
Unilineage dysplasia in ≥ 10% affected
lineage
Of erythroid precursors, < 15% are
ringed sideroblasts
Myeloblasts are not increased (< 5%)
Unicytopenia or bicytopenia of peripheral
blood with < 1% blasts
Unilineage, erythroid dysplasia in ≥ 10%
of red blood cell precursors
Ringed sideroblasts comprise ≥ 15%
nucleated erythroid precursors
Myeloblasts are not increased (< 5%)
Peripheral blood anemia with no blasts
5-9% blasts in the bone marrow and <
5% blasts in the peripheral blood
If < 5% blasts in the bone marrow, then
2-4% blasts in the peripheral blood
Unilineage or multilineage dysplasia
Absence of auer rods
Multiple peripheral blood cytopenias
Peripheral blood with < 1 x 109/L
monocytes
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
Page 6 of 31
Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Table 1. Hematologic disorders and characteristics (cont.)
DISEASE
DIAGNOSTIC CHARACTERISTICS
Refractory Anemia with Excess Blasts
(RAEB-2)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Refractory Cytopenia with Multilineage
Dysplasia (RCMD)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Childhood myelodysplastic syndrome, aka
Refractory Cytopenia of Childhood (RCC)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Myelodysplastic syndrome with isolated
del(5q), aka 5q-syndrome
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Myelodysplastic Syndrome, Unclassifiable
(MDS-U)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
10-19% blasts in the bone marrow or 519% blasts in the peripheral blood
Unilineage or multilineage dysplasia
Auer rods may be present
Multiple peripheral blood cytopenias
Peripheral blood with < 1 x 109/L
monocytes
One or more blood cytopenias with
dysplasia in two or more lines
Multilineage dysplasia in ≥ 10%
precursors
Absence of auer rods
Blasts are not increased (< 5% marrow, <
1% peripheral blood)
Multiple peripheral blood cytopenias
Peripheral blood with < 1 x 109/L
monocytes
Multilineage dysplasia in ≥ 10% of
precursors
Blasts are not increased (< 5% marrow, <
2% peripheral blood)
Dysplastic changes in ≥ 10% of
neutrophils on peripheral blood smear
Peripheral blood anemia
Frequently hypolobated small
megakaryocytes
Blasts are not increased (< 5% blasts in
marrow, < 1% blasts in peripheral blood)
Deletion of part of the long arm of
chromosome 5, del(5q)
Must not meet criteria of any other
specific category
MDS that cannot be classified into any
other defined category due to one or
more atypical features
Examples include:
Hypocellular MDS
MDS with myelofibrosis
< 5% blasts in the marrow with Auer rods
present
MDS with unilineage dysplasia with
associated pancytopenia
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
Page 7 of 31
Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Table 1. Hematologic disorders and characteristics (cont.)
DISEASE
DIAGNOSTIC CHARACTERISTICS
Chronic neutrophilic leukemia
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Chronic eosinophilic leukemia, NOS
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Essential thrombocythemia
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Peripheral blood leukocytosis, ≥ 25 x
109/L with segmented neutrophil > 80%
and immature granulocytes < 10%
Blasts are not increased (< 5% marrow,
< 1% peripheral blood)
Normal granulocytic maturation
No Ph+ or BCR-ABL fusion and no
abnormalities of PDGFRA, PDGFRB, or
FGFR1
Reactive neutrophilia, PV, PMF, ET,
MDS, and MDS/MPN must be ruled out
Peripheral blood eosinophilia ≥ 1.5 x
109/L
Evidence of clonal abnormality but must
not be Ph+ or BCR-ABL fusion,
rearrangement of PDGFRA, PDGFRB, or
FGFR1, or inversion or translocation of
(16)(p13.1,q22)
or
3-19% blasts in the peripheral blood or 619% blasts in the bone marrow.
Reactive and secondary Eosinophilia
must be ruled out
Includes primary thrombocytosis,
idiopathic thrombocytosis, and
hemorrhagic thrombocythemia
Bone marrow with megakaryocytic
hyperplasia; may have minimal fibrosis.
Typically no erythroid or granulocytic
hyperplasia. No ringed sideroblasts or
increased blasts.
JAK2 mutation or other clonal marker
Peripheral blood thrombocytosis, ≥ 450 x
109/L
CML, PMF, PV, MDS, and other myeloid
neoplasms must be ruled out
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Table 1. Hematologic disorders and characteristics (cont.)
DISEASE
DIAGNOSTIC CHARACTERISTICS
Polycythemia Vera (PCV)
Presence of two major and one minor
criterion, or presence of one major and
two minor criterion
Major
Increased hemoglobin (> 18.5 g/dL in
men, > 16.5 g/dL in women)
JAK2 mutation
Minor
Low serum erythropoietin (EPO)
Hypercellular bone marrow with
panmyelosis
In vitro endogenous erythroid colony
formation
Includes chronic idiopathic myelofibrosis
(CIMF), agnogenic* myeloid metaplasia
(AMM), myelofibrosis/sclerosis with
myeloid metaplasia (MMM), and
idiopathic myelofibrosis
Megakaryocytic hyperplasia with fibrosis
(MF 2-3) or hypercellular marrow with
granulocytic hyperplasia
JAK2 mutation or other clonal marker
PV, CML, MDS, and other myeloid
neoplasms must be ruled out
At least two of the following:
splenomegaly, anemia, increased serum
LDH, and leukoerythroblastosis
Definite clinical, laboratory, and
morphological features that fail to meet
criteria for specific MPN classification, or
overlap two or more MPN categories
No Ph+ or BCR-ABL fusion and no
abnormalities of PDGFRA, PDGFRB, or
FGFR1
MPN,U should not be used when clinical
data is insufficient or not available for
proper classification of disease
Blasts and promonocytes < 20% in
peripheral blood and bone marrow
Peripheral blood monocytosis, > 1 x
109/L
Dysplasia in one or more lines; typically
seen, but not an absolute requirement for
diagnosis
No Ph+ or BCR-ABL fusion and no
abnormalities of PDGFRA or PDGFRB
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Primary myelofibrosis
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Myeloproliferative Neoplasm,
Unclassifiable (MPN, U)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Chronic Myelomonocytic Leukemia
(CMMoL)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
Page 9 of 31
Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Table 1. Hematologic disorders and characteristics (cont.)
DISEASE
DIAGNOSTIC CHARACTERISTICS
Juvenile Myelomonocytic Leukemia
(JMML, JCML, JCMML)
If selected, continue with question 16.
Also complete CIBMTR Form 2015.
Atypical chronic myeloid leukemia,
Ph-/BCR- (CML, NOS)
Atypical chronic myeloid leukemia,
Ph-/BCR unknown (CML, NOS)
Atypical chronic myeloid leukemia,
Ph unknown/BCR- (CML, NOS)
Blasts < 20% in bone marrow
Peripheral blood monocytosis,
> 1 x 109/L
No Ph+ or BCR-ABL fusion
Splenomegaly
May exhibit clonal chromosomal
abnormality (may include monosomy 7)
May have GM-CSF hypersensitivity
May have peripheral blood leukocytosis,
> 10 x 109/L
May have increased fetal hemoglobin
Peripheral blood leukocytosis,
≥ 13 x 109/L
Blasts < 20% in peripheral blood and
bone marrow
Dysgranulopoiesis is present in the bone
marrow
Myelodysplastic and myeloproliferative
features
No abnormalities of PDGFRA or
PDGFRB.
No Ph+ or BCR-ABL fusion
Peripheral blood leukocytosis,
≥ 13 x 109/L
Blasts < 20% in peripheral blood and
bone marrow
Dysgranulopoiesis is present in the bone
marrow
Myelodysplastic and myeloproliferative
features
No abnormalities of PDGFRA or
PDGFRB.
No Ph+ and BCR-ABL fusion unknown
Peripheral blood leukocytosis,
≥ 13 x 109/L
Blasts < 20% in peripheral blood and
bone marrow
Dysgranulopoiesis is present in the bone
marrow
Myelodysplastic and myeloproliferative
features
No abnormalities of PDGFRA or
PDGFRB.
Ph chromosome unknown and no BCRABL fusion
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
Page 10 of 31
Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Table 1. Hematologic disorders and characteristics (cont.)
DISEASE
DIAGNOSTIC CHARACTERISTICS
Atypical chronic myeloid leukemia,
Ph unknown/BCR unknown (CML, NOS)
Myelodysplastic/Myeloproliferative
Neoplasm, Unclassifiable (MDS/MPN, U)
If selected, continue with question 16.
Also complete CIBMTR Form 2014.
Aplastic anemia
If selected, continue with question 16.
Also complete CIBMTR Form 2028.
Other hematologic disorder
If selected, specify preceding hematologic
disorder in question 15.
Peripheral blood leukocytosis,
≥ 13 x 109/L
Blasts < 20% in peripheral blood and
bone marrow
Dysgranulopoiesis is present in the bone
marrow
Myelodysplastic and myeloproliferative
features
No abnormalities of PDGFRA or
PDGFRB.
Ph chromosome and BCR-ABL fusion
unknown
Clinical, laboratory, and morphological
features that overlap MPN and MDS; this
includes blasts < 20% in peripheral blood
and bone marrow, platelet count ≥ 450 x
109/L, and WBC ≥ 13 x 109/L
No Ph+ or BCR-ABL fusion and no
abnormalities of PDGFRA, PDGFRB, or
FGFR1
MDS/MPN, U should not be used for
patient with a previous, well-defined MPN
who develop dysplastic features
consistent with transformation to a more
aggressive histology
Markedly hypocellular marrow with
pancytopenia
Peripheral blood cytopenia(s)
Diagnosis of exclusion
If the recipient had an antecedent
hematologic disorder not specified in the
above options, specify in question 15.
* There is a typo on the form; the form should read “agnogenic” rather than angiogenic.
World Health Organization. (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (4th ed.).
Lyon, France.
Question 16: Did the recipient have a predisposing condition prior to the
diagnosis of AML?
A predisposing condition is a condition that contributes to the susceptibility of
developing leukemia. Therefore, diagnosis of the condition increases the
likelihood that the recipient will develop leukemia. If the recipient has a
documented history of a predisposing condition, check “yes” and continue with
question 17. If there is no history of a predisposing condition or predisposition is
unknown, indicate “no” or “unknown” and continue with question 19.
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
Page 11 of 31
Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Questions 17-18: Specify condition.
Bloom syndrome is an autosomal recessive genetic disorder characterized by
excessive chromosome breakage and corresponding rearrangements,
proportional dwarfism, and sun sensitivity. The chromosomal instability seen in
Bloom syndrome is generally assumed to be responsible for these individuals’
predisposition to malignancy.
Down syndrome is also a chromosomal disorder (trisomy 21). It is characterized
by an additional chromosome 21. Down syndrome patients exhibit a particular
set of facial characteristics, growth deficiency, and cognitive impairment.
Although Down syndrome patients have a reduced risk of developing many
common malignancies, they have an increased risk of developing leukemia.
Fanconi anemia is a rare genetic blood disorder that prevents the body from
producing a sufficient number of new blood cells to function properly. Abnormal
blood cells may also be produced. These patients are short in stature, exhibit
skeletal anomalies, and have an increased risk of developing solid tumors and
leukemias.
Neurofibromatosis type 1, also known as von Recklinghausen disease, is an
autosomal dominant genetic disorder characterized by mutation of chromosome
17 resulting in the inactivation of the NF1 gene. This results in abnormal growth
and proliferation of neural crest cells. Patients with neurofibromatosis type 1
often have multiple neurofibromas (benign neural tumors), skeletal abnormalities,
café au lait spots, lisch nodules, freckling in the axilla or groin, and/or optic nerve
glioma. Patients with biallelic inactivation of NF1 may have an increased risk of
developing malignant neoplasms, including rhabdomyosarcoma,
pheochromocytoma, and, in children, myelodysplastic syndrome and acute
leukemia.
Indicate the recipient’s predisposing condition prior to the diagnosis of leukemia.
If AML arose from aplastic anemia or Fanconi anemia, also complete the
associated baseline disease inserts (CIBMTR forms 2028 and 2029,
respectively). If the condition was “other,” specify the condition in question 18.
Laboratory Studies at Diagnosis
Report findings at the time of diagnosis; if multiple studies were performed prior
to the institution of therapy, report the latest values prior to the start of treatment.
Questions 19-21: WBC
Indicate whether the white blood count (WBC) was “known” or “unknown” at the
time of AML diagnosis. If “known,” report the laboratory count and unit of
measure documented on the laboratory report in question 20; indicate the date
sample was collected in question 21. If “unknown,” continue with question 22.
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
Version 2.1 (02/07/2014)
Page 12 of 31
Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Questions 22-24: Blasts in blood
Indicate whether the percentage of blasts in the peripheral blood was “known” or
“unknown” at the time of AML diagnosis. If “known,” report the percentage
documented on the laboratory report in question 23; indicate the date sample
was collected in question 24. If “unknown,” continue with question 25.
NOTE:
If a differential was performed and there were no blasts present in the peripheral
blood, the laboratory report may not display a column for blasts. In this case, it
can be assumed that no blasts were present and “0” can be entered on the form.
Blast counts obtained by flow cytometry should be reflected under the flow
cytometry data fields; only report percentage blasts as determined by peripheral
blood differential.
Questions 25-27: Blasts in bone marrow
Indicate whether the percentage of blasts in the bone marrow was “known” or
“unknown” at the time of AML diagnosis. If “known,” report the percentage
documented on the laboratory report in question 26; indicate the date sample
was collected in question 27. If “unknown,” continue with question 28.
NOTE:
If the bone marrow pathology report states a range for blasts, enter the average
of the range rounded to the nearest whole number (e.g., if 0-5%, enter 3%).
If the report indicates “sheets of blasts” or “packed marrow,” report 100%.
If the report states > n% blasts, enter (n+1)% on the form. For example, if the
laboratory report indicates > 90% blasts, report 91%.
If the report states <n% blasts, enter (n-1)% on the form. For example, if the
laboratory report indicates <5% blasts, report 4%.
Question 28: Was extramedullary disease present?
Extramedullary refers to disease found in organs or tissue outside the bone
marrow or blood stream (e.g., central nervous system, testes, skin, soft tissue,
etc.). Examples of extramedullary disease in AML patients include granulocytic
sarcoma, subcutaneous nodules, leukemia cutis, and meningeal leukemia. If
there is evidence of extramedullary disease at the time of diagnosis, indicate
“yes” and continue with question 29. If there is no evidence of extramedullary
disease at the time of diagnosis, indicate “no” and continue with question 36. If
the status of extramedullary sites at the time of diagnosis is unknown, indicate
“unknown” and continue with question 36.
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Questions 29-35: Specify site(s) of extramedullary disease.
Indicate all sites of extramedullary disease. If question 28 was answered “yes,”
then each of questions 29-34 must be answered as “yes” or “no.” If question 34,
“other” site of extramedullary disease is answered “yes,” specify site in question
35.
Question 36: Were cytogenetics tested (conventional or FISH)?
Cytogenetic analysis is the study of chromosomes. Cytogenetic assessment
involves testing blood or bone marrow for the presence of a known chromosomal
abnormality that reflects the recipient’s disease. Testing methods you may see
include conventional chromosome analysis (karyotyping), fluorescence in situ
hybridization (FISH), or microarray comparative genomic hybridization (aCGH)
testing. For more information about cytogenetic testing and terminology, see
Appendix R, Cytogenetic Abbreviations and Terminology.
Table 2. Examples of AML cytogenetic findings categorized by prognosis
FAVORABLE
t(15;17)
t(8;21)
inv(16) or t(16;16)
INTERMEDIATE
Normal
+8
t(9;11)
All other abnormalities
POOR
≥ 3 abnormalities
5- or 5q7- or 7qt(9;22)
Indicate if cytogenetic studies were obtained at the time the recipient was
diagnosed with AML or prior to the start of treatment.
If cytogenetic studies were obtained, check “yes” and continue with question 37.
If cytogenetic studies were not obtained or it is unknown if chromosome studies
were performed, indicate “no” or “unknown” and continue with question 76.
Question 37: Date sample collected
Report the date the sample was collected for cytogenetic or FISH testing. If
multiple studies were performed prior to the start of therapy, report the latest
assessment prior to the start of treatment.
If the exact date is not known, use the process for reporting partial or unknown
dates as described in General Instructions, Guidelines for Completing Forms.
Question 38: Results of test
If cytogenetic studies identified abnormalities (any karyotype other than 46XX or
46XY), indicate “abnormalities identified” and continue with question 39.
If cytogenetic studies yielded no evaluable metaphases or there were no
abnormalities identified, indicate such and continue with question 76.
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Questions 39-74: Specify abnormalities
If question 38 indicates that abnormalities were identified, each of questions 3973 must be answered as “yes” or “no.” Do not leave any response blank. Indicate
“yes” for each cytogenetic abnormality identified at diagnosis or prior to the start
of first therapy; indicate “no” for all options not identified on cytogenetic
assessment at diagnosis or prior to the start of first therapy. If one or more
abnormalities are best classified as “other abnormality,” specify in question 74.
If ≥ 3 cytogenetic abnormalities were identified at the time of AML diagnosis or
prior to the start of first therapy, select “yes” for question 72 (complex, ≥ 3 distinct
abnormalities) and specify the corresponding abnormalities in questions 39-71. If
any of these abnormalities are not listed among 39-71, report “other abnormality,”
and specify in question 74. For example, if the karyotype included -7, +8, and -13,
report “yes” for questions 40, 46, 72, and 73/74. Complete the remaining
indicators as “no,” and do not leave any response blank.
Question 75: Was documentation submitted to the CIBMTR (e.g.,
cytogenetic or FISH report)?
Indicate if a copy of the cytogenetic or FISH report is attached. Use the Log of
Appended Documents (Form 2800) to attach a copy of the cytogenetic or FISH
report. Attaching a copy of the report may prevent additional queries.
Question 76: Were tests for molecular markers performed (e.g., PCR)?
Molecular assessment involves testing blood or bone marrow for the presence of
known molecular markers associated with the recipient’s disease. Molecular
assessments are the most sensitive test for genetic abnormalities and involve
amplifying regions of cellular DNA by polymerase chain reaction (PCR), typically
utilizing RNA to generate complementary DNA through reverse transcription (RTPCR).
Indicate if molecular studies were obtained at the time the recipient was
diagnosed with AML or prior to the start of treatment.
If molecular studies were obtained, check “yes” and continue with question 77.
If molecular studies were not obtained or it is unknown if molecular studies were
performed, indicate “no” or “unknown” and continue with question 88.
Question 77: Date sample collected
Report the date the sample was collected for molecular testing.
If the exact date is not known, use the process for reporting partial or unknown
dates as described in General Instructions, Guidelines for Completing Forms.
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Questions 78-86: Specify abnormalities.
If question 76 indicates that molecular markers were identified, then each of
questions 78-85 must be answered as “positive,” “negative,” or “not done.” Do
not leave any response blank. If question 85 is answered “positive,” specify the
identified molecular marker in question 86. Duplicate questions 85-86 if more
than one “other molecular marker” is identified.
Table 3. Common molecular markers associated with AML
MOLECULAR ABNORMALITY
CHARACTERISTICS
CEBPA
CEBPA, aka CCAAT/enhancer binding protein α,
is a transcription factor required for the
differentiation of granulocytes. Numerous CEBPA
mutations have been identified in relation to AML,
with the majority of patients displaying biallelic
mutations ultimately resulting in the down
regulation of gene activity. Decreased gene
activity results in decreased differentiation
potential for immature granulocytes. An
estimated 7-15% of AML patients have CEBPA
mutations and CEBPA mutations are generally
found in M1 and M2 subtypes in conjunction with
intermediate-risk cytogenetics. Studies show an
association with more favorable outcomes.
Lin L, Chen C, Lin D, Tsay W, Tang J, Yeh Y, Shen H, Su F, Yao M,
Huang S, Tien H. (2005). Characterization of CEBPA Mutations in
Acute Myeloid Leukemia: Most patients with CEBPA mutations have
biallelic mutations and show a distinct immunophenotype of the
leukemic cells. Clin Cancer Res, 11, 1372-9.
FLT3-D835 point mutation
FLT3 encodes a receptor tyrosine kinase. The
FLT3-D835 point mutation, aka FLT3-TKD, is an
activating mutation impacting tyrosine-kinase
domains. FLT3 mutations are found in up to 1/3
of all AML patients. The clinical significance of
TKD activation remains unclear. FLT3-D385
mutations are often found in conjunction with
other mutations. Overall, FLT3-D385 is not
considered a favorable or poor prognostic
indicator. However, in certain combinations with
other mutations, there are associations with both
improved and diminished survival.
Mead AJ, Linch DC, Hills RK, Wheatley K, Burnett AK, Gale RE.
(2007). FLT3 tyrosine kinase domain mutations are biologically
distinct from and have a significantly more favorable prognosis than
FLT3 international tandem duplications in patient with acute myeloid
leukemia. Blood, 110, 1262-70.
Whitman SP, Ruppert AS, Radmacher, MD, et al. (2008). FLT3
D835/I836 mutations are associated with poor disease-free survival
and a distinct gene-expression signature among younger adults with
de novo cytogenetically normal acute myeloid leukemia lacking
FLT3 internal tandem duplications. Blood, 111, 1552-59.
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Table 3. Common molecular markers associated with AML (cont.)
MOLECULAR ABNORMALITY
CHARACTERISTICS
FLT3-ITD mutation
FLT3 encodes a receptor tyrosine kinase. The
FLT3-ITD (internal tandem duplication) interferes
with certain down regulation functions within
receptor tyrosine kinases, leading to activation of
TK activity. FLT3 mutations are found in up to 1/3
of all AML patients. FLT3-ITD is considered a
poor prognostic factor. Sorafenib (Nexavar) has
been shown to initially improve disease response
in FLT3-ITD-positive AML.
Man CH, Fung TK, Ho C, et al. (2011). Sorafenib treatment of FLTITD+ acute myeloid leukemia: favorable initial outcome and
mechanisms of subsequent non-responsiveness associated with the
emergence of a D835 mutation. Blood, 119 (22), 5133-43.
IDH1
Isocitrate Dehydrogenase (IDH) is an oxidative
enzyme involved in the citric acid cycle. IDH1
mutations result in incorrect catalytic activity,
leading to increased levels of an oncometabolite,
2-hydroxyglutarate. The pathologic activity of
IDH1 mutations is still being studied, but it has
been suggested that IDH mutations may be a
distinct mechanism in AML pathogenesis;
research models show they may cause an
accumulation of hematopoietic progenitor cells.
Early research suggests IDH1 mutation may be a
less favorable prognostic indicator.
Marucci G, Maharry K, Wu YZ, et al. (2010). IDH1 and IDH2 Gene
Mutations Identify Novel Molecular Subsets Within De Novo
Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and
Leukemia Group B Study. J Clin Oncol, 28(14), 2348-55.
IDH2
Isocitrate Dehydrogenase (IDH) is an oxidative
enzyme involved in the citric acid cycle. IDH2 is a
mitochondrial homolog to IDH1. Much like IDH1
mutations, IDH2 mutations result in incorrect
catalytic activity, leading to increased levels of
(D)-2-hydroxyglutarate. The pathologic activity of
IDH2 mutations are still being studied, but it has
been suggested that IDH mutations may be a
distinct mechanism in AML pathogenesis;
research models show they may cause an
accumulation of hematopoietic progenitor cells.
Early research suggests IDH2 mutation may be a
more favorable prognostic indicator, unlike IDH1
mutation, though there may be differences based
on where the IDH2 mutation occurs in gene.
Green CL, Evans CM, Zhao L, et al. (2011).The prognostic
significance of IDH2 mutations in AML depends on the location of
the mutation. Blood, 118(2), 409-12.
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Table 3. Common molecular markers associated with AML (cont.)
MOLECULAR ABNORMALITY
CHARACTERISTICS
KIT
KIT encodes a receptor tyrosine kinase. The KIT
mutations at exons 8 and 17 are associated with
activation of encoded proteins, resulting in
activation impacting tyrosine-kinase domains.
Patients with t(8;21) and inv(16) cytogenetics are
frequently screened for KIT mutations, which
adversely affect prognosis in these patients.
Döhner K, Döhner H. (2008).Molecular characterization of acute
myeloid leukemia. Haematologica, 93(7), 976-82.
NPM1
NPM1 encodes a protein responsible for multiple
cellular functions, including the regulation of the
ARF-p53 tumor suppressor pathway. Mutations
in NPM1 result in gene over-expression and
subsequent inactivation of ARF-p53 tumor
suppression pathway. NPM1 mutations are one
of the most common molecular markers seen in
AML and are associated with improved survival.
Varhaak RGW, Goudswaard CS, van Putten W, et al.
(2005).Mutations in nucleophosmin (NPM1) in acute myeloid
leukemia (AML): association with other gene abnormalities and
previously established gene expression signatures and their
favorable prognostic significance. Blood, 106(12), 3747-54.
Other molecular marker
Assessments for other molecular markers known
or believed to be associated with AML may be
performed. If these studies are performed,
indicate “yes” and specify in question 86.
Question 87: Was documentation submitted to the CIBMTR?
Indicate if a copy of the molecular report(s) is attached. Use the Log of Appended
Documents (Form 2800) to attach a copy of the molecular report. Attaching a
copy of the report may prevent additional queries.
Pre-HCT Therapy
Complete a “Line of Therapy” section for each line of therapy administered prior
to the start of the preparative regimen. If multiple lines of therapy were
administered, copy and complete questions 89-125 for each line of therapy.
Question 88: Was therapy given?
Indicate if the recipient received treatment for AML after the time of diagnosis
and before the start of the preparative regimen. If “yes,” continue with question
89. If “no”, continue with question 126. For recipients with MDS that transformed
to AML, only report therapy given after the transformation to AML; any treatments
given prior to the transformation would be reported on the MDS Pre-HCT Data
form (Form 2014).
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Question 89: Purpose of therapy
Indicate the purpose of the therapy administered between the time of AML
diagnosis and the start of the preparative regimen.
Chemotherapy is initially given as induction therapy intended to bring the disease
into remission. Recipients usually have one to two cycles of induction therapy;
disease prognosis is considered less favorable if the patient fails to achieve
remission with first induction therapy and is even poorer in patients failing two or
more induction therapies.1 An example of a common induction therapy for all
AML subtypes except M3 is a combination of an anthracycline and cytarabine,
commonly known as “7+3.” In this regimen, cytarabine is typically administered
for seven days at a dose of 100 mg/m2/day. The anthracycline (usually
daunorubicin at 45 to 60 mg/m2/day or idarubicin at 12 mg/m2/day) is generally
given on the first three days the cytarabine is given.
The second phase of chemotherapy is known as consolidation therapy. The goal
of consolidation therapy is to destroy any remaining leukemia cells and sustain
remission. An example of a common consolidation therapy for all AML subtypes
except M3 is high-dose cytarabine, commonly referred to as “HiDAC.” In this
regimen, cytarabine is typically administered at a dose exceeding 10 g/m 2 per
cycle.
Maintenance chemotherapy may follow consolidation therapy; maintenance
chemotherapy is given in lower doses and is intended to prolong a remission.
Maintenance therapy is used less commonly for the treatment of AML than other
malignancies. Treatment may also be administered for relapsed disease. Much
like induction therapy, treatment for relapse is intended to bring the disease back
into remission. Systemic therapeutic agents used to induce remission following
relapse often differ from those used in the initial induction, since the disease is
often resistant to many of the agents used earlier in the disease course and is
considered high-risk with a poor prognosis. Allogeneic HCT is often considered
the only potential “cure” for relapsed disease.
1
Ravandi F, Cortes J, Faderl S, O’Brien S, Garcia-Manero G, Verstovesek S, Santos F, Shan J, Brandt M, de Lima M,
Pierce S, Kantarjian H. (2010). Characteristics and outcome of patients with acute myeloid leukemia refractory to one
cycle of high-dose cytarabine-based induction therapy. Blood, 116(26), 5818-23.
Question 90: Systemic therapy
Systemic therapy refers to a delivery mechanism where a therapeutic agent is
delivered orally or intravenously, enters the bloodstream, and is distributed
throughout the body. Intrathecal therapy is administered via injection into the
subarachnoid space; these drugs reach the cerebral spinal fluid and act on the
central nervous system.
Indicate “yes” if the patient received systemic or intrathecal therapy and continue
with question 91.
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If the patient did not receive systemic or intrathecal therapy, indicate “no” and
continue with question 114.
Questions 91-92: Date therapy started
Indicate “known” if the therapy start date is documented and specify the date
systemic therapy was first administered in question 92. If the date is unknown,
indicate such and continue with question 93.
Questions 93-94: Date therapy stopped
Indicate “known” if the therapy completion date is documented and specify the
date the therapy stopped in question 94. If the patient is receiving systemic
therapy in cycles, specify the first day of the last cycle of systemic therapy. If
the patient is receiving a single line or single administration, indicate the last day
systemic therapy was administered.
If the date is unknown, indicate such and continue with question 95.
Questions 95-96: Number of cycles
Indicate if the number of cycles is “known” or “unknown.” If the number of cycles
is known, continue with question 96 and specify the number of cycles of
chemotherapy administered. If the patient is receiving a single administration or
one line of chemotherapy, indicate a single cycle.
If the number of cycles is unknown, continue with question 97.
Questions 97-113: Specify systemic or intrathecal therapy agents
Systemic therapy agents and treatment regimens vary based on disease,
prognosis, and protocol. Drugs may be administered in an inpatient or outpatient
setting, and treatment may consist of one or multiple drugs. Additionally, drugs
may be administered on a single day, over consecutive days, or continuously.
Indicate “yes” or “no” for each chemotherapy drug listed. Do not leave any
response blank. If the recipient received a chemotherapy agent that is not listed,
check “yes” for “other systemic therapy” and specify the treatment in question
113.
NOTE: Reporting Cytarabine doses (Questions 101 & 102)
In some cases the dose of cytarabine administered for treatment may not be
available. Generally, low- to intermediate-dose Ara-C is considered
≤ 10 g/m2/cycle, as is commonly seen in standard “7+3” induction. High dose
Ara-C is considered > 10 g/m2/cycle, as is commonly seen in “HiDAC” therapy.
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NOTE: Reporting Intrathecal Therapy (Question 108)
Any intrathecal therapy administered as part of a pre-HCT line of therapy should
be reported only in the “intrathecal therapy” category (question 108) and not in its
corresponding drug category. For example, if intrathecal cytarabine is
administered as part of a pre-HCT line of therapy and the patient does not
receive systemic cytarabine, questions 101-102 are answered “no”, and question
108 is answered “yes.” It is not necessary to specify the intrathecal agent in
question 113.
Question 114: Radiation therapy
Radiation therapy uses high-energy, ionizing radiation to kill malignant cells.
However, much like non-targeted systemic therapy, radiation therapy does not
specifically target malignant cells and does have significant side effects. For that
reason, high-dose radiation often targets a limited field. Radiation therapy is not
typically used in the treatment of AML and is generally reserved for the treatment
of brain, spinal fluid, or testicular involvement.
Indicate if the recipient received radiation treatment for AML after the time of
diagnosis and before the start of the preparative regimen. If “yes,” continue with
question 115. If “no”, continue with question 122.
Question 115: Date therapy started
Indicate “known” if the radiation therapy start date is documented, continue with
question 116 and specify the first date of radiation administration. If the date is
unknown, indicate such and continue with question 117.
Question 117: Date therapy stopped
Indicate “known” if the radiation therapy completion date is documented, continue
with question 118 and specify the last date of radiation administration. If the date
is unknown, indicate such and continue with question 119.
Questions 119-121: Specify site(s) of radiation therapy
Indicate “yes” or “no” for each radiation site. Do not leave any response blank.
Question 119 asks if radiation was delivered to the central nervous system; the
central nervous system consists of the brain and spinal cord. If the recipient
received radiation to any other site, indicate “yes” for question 120 and specify
the site in question 121.
Question 122: Best Response to Line of Therapy
Complete hematologic response (CR) is a treatment response where all of the
following criteria are met for at least four weeks:
< 5% blasts in the bone marrow
Normal maturation of all cellular components in the bone marrow
No blasts with Auer rods
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No extramedullary disease (e.g., central nervous system or soft tissue
involvement)
ANC of > 1,000/µL
Platelets ≥ 100,000/µL
Transfusion independent
Include recipients with persistent cytogenetic or molecular testing abnormalities
who otherwise meet all criteria of hematologic CR. Recipients with persisting
extramedullary disease are not considered to be in CR.
Indicate if the patient’s best response to this line of therapy was a complete
remission or was not a complete remission.
Question 123: Date assessed
Enter the date the best response to the line of therapy was established. Report
the date of the pathological evaluation (e.g., bone marrow biopsy); if no
pathologic evaluation was reported, report the date of blood/serum assessment
(e.g., CBC, peripheral blood smear). Enter the date the sample was collected for
pathological and/or laboratory evaluation. If the recipient was treated for
extramedullary disease and a radiological assessment (e.g., X-ray, CT scan, MRI
scan, PET scan) was performed to assess disease response, enter the date the
imaging took place. If no pathological, radiographic, or laboratory assessments
were performed to establish the best response to the line of therapy, report the
office visit in which the physician clinically assessed the recipient’s response.
If the exact date is not known, use the process for reporting partial or unknown
dates as described in General Instructions, Guidelines for Completing Forms.
Question 124: Did the recipient relapse following this line of therapy?
Relapse is the recurrence of disease after CR. AML relapse is demonstrated by
one or more of the following findings:
≥ 5% blasts in the marrow and/or peripheral blood
Extramedullary disease evident upon radiographic examination
Disease presence determined by a physician upon clinical assessment
Indicate if relapse occurred following the line of therapy being reported.
Question 125: Date of relapse
Enter the date that relapse was established following the line of therapy. If
reporting a pathological evaluation (e.g., bone marrow) or blood/serum
assessment (e.g., CBC, peripheral blood smear), enter the date the sample was
collected. If extramedullary disease was detected upon radiographic examination
(e.g., X-ray, CT scan, MRI scan, PET scan), enter the date the imaging took
place. If the physician determines evidence of relapse following a clinical
assessment during an office visit, report the date of assessment.
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If the exact date is not known, use the process for reporting partial or unknown
dates as described in General Instructions, Guidelines for Completing Forms.
Question 126: Did the recipient have central nervous system leukemia at
any time prior to the start of the preparative regimen?
Central nervous system leukemia is a disease of the leptomeninges, membranes
that surround the brain and spinal cord. Indicate if the recipient had central
nervous system involvement by AML at any time between the AML diagnosis and
prior to the start of the preparative regimen. In the absence of a negative CSF
assessment, lack of neurological signs and symptoms documented throughout
the patient’s disease course is sufficient to indicate that the recipient never had
central nervous system leukemia. If the patient’s CNS status was unknown at
any time prior to the start of the preparative regimen, indicate “unknown.” If the
patient never had a CNS evaluation (e.g., CSF) and it is not clear that the patient
never had neurological signs and symptoms, indicate “unknown.”
Laboratory Studies at Last Evaluation Prior to the Start of the
Preparative Regimen
These questions are intended to determine the hematological status of the
recipient prior to the preparative regimen. Testing may be performed multiple
times within the pre-transplant work-up period (approximately 30 days) prior to
the start of the preparative regimen; report the most recent laboratory values.
Laboratory values obtained on the first day of the preparative regimen may be
reported as long as the sample was drawn before any radiation or systemic
therapy was administered.
Questions 127-129: WBC
Indicate whether the white blood count (WBC) was “known” or “unknown”
immediately prior to the start of the preparative regimen. If “known,” report the
laboratory count and unit of measure documented on the laboratory report in
question 128; indicate the date the sample was collected in question 129. If
“unknown,” continue with question 130.
Questions 130-132: Blasts in blood
Indicate whether the percentage of blasts in the peripheral blood was “known” or
“unknown” immediately prior to the start of the preparative regimen. If “known,”
report the percentage documented on the laboratory report in question 131;
indicate the date the sample was collected in question 132. If “unknown,”
continue with question 133.
NOTE:
If a differential was performed and there were no blasts present in the peripheral
blood, the laboratory report may not display a column for blasts. In this case, it
can be assumed that no blasts were present and “0” can be entered on the form.
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Blasts quantified in the peripheral blood by flow cytometry are captured
separately in question 187.
Questions 133-135: Blasts in bone marrow
Indicate whether the percentage of blasts in the bone marrow was “known” or
“unknown” immediately prior to the start of the preparative regimen. If “known,”
report the percentage documented on the laboratory report in question 134;
indicate the date sample was collected in question 135. If “unknown,” continue
with question 136.
NOTE:
If the bone marrow pathology report states a range for blasts, enter the average
of the range rounded to the nearest whole number (e.g., if 0-5%, enter 3%).
If the report indicates “sheets of blasts” or “packed marrow,” report 100%.
If the report states > n% blasts, enter (n+1)% on the form. For example, if the
laboratory report indicates > 90% blasts, report 91%.
If the report states < n% blasts, enter (n-1)% on the form. For example, if the
laboratory report indicates < 5% blasts, report 4%.
Question 136: Were cytogenetics tested (conventional or FISH)?
Cytogenetic assessment involves testing blood or bone marrow for the presence
of a known chromosomal abnormality that reflects the recipient’s disease. Testing
methods include conventional chromosome analysis (karyotyping), fluorescence
in situ hybridization (FISH), and microarray comparative genomic hybridization
(aCGH) testing.
Indicate if cytogenetic studies were obtained immediately prior to the start of the
preparative regimen.
If cytogenetic studies were obtained, check “yes” and continue with question 137.
If cytogenetic studies were not obtained or it is unknown if chromosome studies
were performed, indicate “no” or “unknown” and continue with question 175.
Question 137: Date sample collected
Report the date sample was collected for cytogenetic or FISH testing.
Question 138: Results of tests
If cytogenetic studies identified abnormalities (any karyotype other than 46XX or
46XY), indicate “abnormalities identified” and continued with question 139.
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If cytogenetic studies yielded no evaluable metaphases or there were no
abnormalities identified, indicate such and continue with question 175.
Questions 139-174: Specify abnormalities.
If question 138 indicates that abnormalities were identified, each of questions
139-173 must be answered as “yes” or “no.” Do not leave any response blank.
Indicate “yes” for each cytogenetic abnormality identified at the last evaluation
prior to the start of the preparative regimen in questions 139-173; indicate “no”
for all options not identified on cytogenetic assessment prior to the start of the
preparative regimen. If one or more abnormalities are best classified as “other
abnormality,” specify in question 174.
If ≥ 3 cytogenetic abnormalities were identified at the last evaluation prior to the
start of the preparative regimen, select “yes” for question 172 (complex, ≥ 3
distinct abnormalities) and specify the corresponding abnormalities in questions
139-171. If any of these abnormalities are not listed among 139-171, report
“other abnormality,” and specify in question 174. For example, if the karyotype
included -7, +8, and -13, report “yes” for questions 140, 146, 172, and 173/174.
Complete the remaining indicators as “no,” and do not leave any response blank.
Question 175: Were tests for molecular markers performed (e.g., PCR)?
Molecular assessment involves testing blood or bone marrow for the presence of
known molecular markers associated with the recipient’s disease. Molecular
assessments are the most sensitive test for genetic abnormalities and involve
amplifying regions of cellular DNA by polymerase chain reaction (PCR), typically
utilizing RNA to generate complementary DNA through reverse transcription (RTPCR).
Indicate if molecular studies were obtained immediately prior to the start of the
preparative regimen.
If molecular studies were obtained, check “yes” and continue with question 176.
If molecular studies were not obtained or it is unknown if molecular studies were
performed, indicate “no” or “unknown” and continue with question 186.
Question 176: Date sample collected
Report the date the sample was collected for molecular testing.
Questions 177-185: Specify abnormalities
If question 175 indicates that molecular markers were identified, then each of
questions 177-184 must be answered as “positive,” “negative,” or “not done.” Do
not leave any response blank. If question 184 is answered “positive,” specify the
molecular marker identified in question 185.
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See Table 3 in this manual for additional information on common molecular
markers associated with AML.
Question 186: Was flow cytometry performed?
Flow cytometry assessment is a method of analyzing peripheral blood, bone
marrow, or tissue preparations for multiple unique cell characteristics. Its primary
clinical purpose in the setting of leukemias is to quantify blasts in the peripheral
blood or bone marrow, or to identify unique cell populations through
immunophenotyping. Flow cytometry assessment may also be referred to as
“MRD,” or minimal residual disease, testing.
Indicate if flow cytometry was performed on a peripheral blood and/or bone
marrow sample immediately prior to the start of the preparative regimen.
If flow cytometry was performed, check “yes” and continue with question 187.
If flow cytometry was not performed or it is unknown if flow cytometry was
performed, indicate “no” or “unknown” and continue with question 193.
Question 187: Blood
Indicate if flow cytometry was performed on peripheral blood immediately prior to
the start of the preparative regimen.
If flow cytometry was performed on a peripheral blood sample, check “yes” and
continue with question 188.
If flow cytometry was not performed or it is unknown if flow cytometry was
performed, indicate “no” or “unknown” and continue with question 190.
Question 188: Date sample collected
Report the date the peripheral blood sample was collected for flow cytometry
analysis.
Question 189: Was disease detected?
Indicate if evidence of disease was detected in the peripheral blood sample sent
for flow cytometry analysis. Evidence of disease may include the presence of
blasts or an immunophenotype known to characterize the patient’s disease.
If flow cytometry results were consistent with evidence of disease, check “yes.”
If flow cytometry results were not consistent with continued evidence of disease,
check “no.”
Question 190: Bone marrow
Indicate if flow cytometry was performed on bone marrow immediately prior to
the start of the preparative regimen.
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
If flow cytometry was performed on a bone marrow sample, check “yes” and
continue with question 191.
If flow cytometry was not performed or it is unknown if flow cytometry was
performed, indicate “no” or “unknown” and continue with question 193.
Question 191: Date sample collected
Report the date bone marrow sample was collected for flow cytometry analysis.
Question 192: Was disease detected?
Indicate if evidence of disease was detected in the bone marrow sample sent for
flow cytometry analysis. Evidence of disease may include the presence of blasts
or an immunophenotype known to characterize the patient’s disease.
If flow cytometry results were not consistent with continued evidence of disease,
check “no.”
Disease Status at Last Evaluation Prior to the Start of the
Preparative Regimen
Question 193: What was the disease status based on hematologic test
results?
Indicate the disease status of AML at the last evaluation prior to the start of the
preparative regimen.
If “1st complete remission,” “2nd complete remission,” “≥ 3rd complete
remission,” or “no treatment” is indicated, continue with question 201.
If “primary induction failure,” “1st relapse,” “2nd relapse,” or “≥ 3rd relapse” is
indicated, continue with question 194.
Table 4. Disease status criteria for AML
DISEASE STATUS
DEFINITION
Primary Induction Failure (PIF)
The patient received treatment for AML but never
achieved complete remission at anytime. PIF is
not limited by the number of unsuccessful
treatments; this disease status only applies to
recipients who have never been in complete
remission.
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Table 4. Disease status criteria for AML (cont.)
DISEASE STATUS
Complete Remission (CR)
DEFINITION
Hematologic complete remission is defined as
meeting all of the following response criteria for at
least four weeks.
< 5% blasts in the bone marrow
No blasts with Auer rods
Normal maturation of all cellular
components in the bone marrow
No extramedullary disease (e.g., CNS, soft
tissue disease)
Neutrophils ≥ 1,000/µL
Platelets ≥ 100,000/µL
Transfusion independent
In some cases, there may not be a four-week
interval between completion of therapy and the
pre-transplant disease assessment; in this case,
CR should still be reported as the status at
transplant, since it represents the “best
assessment” prior to HCT. This is an exception to
the criteria that CR be durable beyond four weeks;
the pre-transplant disease status should not be
changed based on early relapse or disease
assessment post-transplant.
Include recipients with persistent cytogenetic or
molecular abnormalities who meet the above CR
criteria for hematologic CR.
Include recipients meeting the above CR criteria
regardless of how many courses of therapy were
required to achieve CR.
NOTE for recipients with MDS that transformed to
AML: If the recipient has residual MDS following
treatment for AML, report the AML disease status
as either PIF or relapse (i.e., the recipient cannot
be in an AML CR if there is evidence of MDS at
the time of assessment).
The number of this complete remission can be
determined by using the following guidelines:
1st CR: no prior relapse
2nd CR: one prior relapse
3rd or higher: two or more prior relapses
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
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Table 4. Disease status criteria for AML (cont.)
DISEASE STATUS
Relapse (REL)
No Treatment
DEFINITION
Relapse is defined as the recurrence of disease
after CR, meeting the following criteria:
≥ 5% blasts in the marrow or peripheral
blood
Extramedullary disease
Disease presence determined by a
physician upon clinical assessment
The number of this relapse can be determined by
using the following guidelines:
1st relapse: one prior CR
2nd relapse: two prior CRs
3rd or higher: three or more CRs
Do not include a partial response (PR) when
determining number of relapse. Recipients who
achieve a PR to treatment should be classified as
either PIF or relapse; PR in AML is generally of
short duration and is unlikely to predict clinical
benefit.
The recipient was diagnosed with acute leukemia
and never received therapeutic agents; include
patients who have received only supportive
therapy, including growth factors and/or blood
transfusions.
NOTE for recipients with MDS that transformed to
AML: “No treatment” may apply if the recipient’s
MDS was treated, then transformed to AML, and
the recipient proceeded directly to transplant
without receiving treatment for their AML.
Questions 194-200: Specify which of the following [sites] showed active
leukemia at last evaluation prior to the start of the preparative regimen
Indicate “yes,” “no,” or “unknown” for each site specified in questions 194-199.
Do not leave any response blank. If “yes” is indicated for “other site,” specify the
site in question 200. If the patient is not in complete remission, at least one of
questions 194-199 must be answered “yes.”
Question 201: Date assessed
Enter the date of the most recent assessment of disease status prior to the start
of the preparative regimen. The date reported should be that of the most
disease-specific assessment within the pre-transplant work-up period
(approximately 30 days). Clinical and hematologic assessments include
pathological evaluation (e.g., bone marrow biopsy), radiographic examination
(e.g., X-ray, CT scan, MRI scan, PET scan), and laboratory assessment (e.g.,
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
CBC, peripheral blood smear), in addition to clinician evaluation and physical
examination. Enter the date the sample was collected for examination for
pathological and laboratory evaluations; enter the date the imaging took place for
radiographic assessments.
If the exact date is not known, use the process for reporting partial or unknown
dates as described in General Instructions, Guidelines for Completing Forms.
Signature
The FormsNet3SM application will automatically populate the signature data
fields, including name and email address of person completing the form and date
upon submission of the form.
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Instructions for Acute Myelogenous Leukemia (AML) Pre-HCT Data
CIBMTR Form 2010
Manual Change History
Version
Number
Date of
Change
2.1
2.1
02/07/2014
02/07/2014
Type of Change
(Add / Remove /
Modify)
Add
Remove
2.1
02/07/2014
Remove
Description of Change
Added “Revision 3” to the title of the document
Removed “Reappearance of cytogenetic
abnormalities and/or molecular markers associated
with the diagnosis that, in the judgment of a
physician, are at a level representing relapse” from
the bulleted list in the explanatory text of question
124.
Removed “If the physician determines cytogenetic
or molecular relapse, enter the date of sample
collection for cytogenetic or molecular evaluation”
from the explanatory text of question 125.
© 2013 National Marrow Donor Program ® and The Medical College of Wisconsin
Document Title: CIBMTR Forms Manual: Acute Myelogenous Leukemia Pre-HCT Data Form 2010
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