From www.bloodjournal.org by guest on November 17, 2014. For personal use only. 1992 79: 2799-2800 Clinical relevance of acute mixed-lineage leukemia [letter; comment] F Ferrara and L Del Vecchio Updated information and services can be found at: http://www.bloodjournal.org/content/79/10/2799.citation.full.html Articles on similar topics can be found in the following Blood collections Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved. From www.bloodjournal.org by guest on November 17, 2014. For personal use only. CORRESPONDENCE 2799 CLINICAL RELEVANCE OF ACUTE MIXED-LINEAGE LEUKEMIA have been the results if only CD7+/CD2+ patients had been analyzed? Furthermore, it is noteworthy that in Pui et al’s series four Ly+ AML cases who failed AML induction therapy subseA recent report by Pui et all focused on the biologic and clinical quently entered CR with prednisone, vincristine, and L-Asparagirelevance of acute mixed-lineage leukemia; namely, acute lymphonase (a quite unusual chemotherapy program for classical AML). blastic leukemia expressing myeloid-associated antigens (My+ The outcome for the CD7+/CD2+ AML cases probably would ALL) and acute myeloid antigens expressing lymphoid antigens have been different if this approach had not been used. In our (Ly+ AML) were analyzed in a pediatric series. In our opinion, a opinion, the analytical subtyping of AML on the basis of T-cell major point in the field of hybrid acute leukemia remaining antigen ectopic expression needs further investigating. For examundetermined is which “ectopic” antigens and what level of ectopic ple, different combinations of T-cell antigens (eg, CD7, CD2, CD5, expression significantly affect the clinical outcome. The findings CD6) on AML blasts may represent quite distinct biological regarding My+ ALL are quite controversial? On the contrary, phenomena, possibly corresponding to different hemopoietic steps. T-cell antigens expression in AML seems to characterize a distinct In this respect, we consider CD7+/CD2+ AML to be a distinct clinical entity in both children and ad~lts.3.~ From an analysis of clinico-hematologic entity sharing, in an extremely balanced fash107 AML samples, we demonstrated that CD7 and CD2 simultaion, both myeloid and lymphoid features. We feel that these neous expression on myeloid blasts is a nonrandom event, recurpatients should be allocated to unique clinical trials using comring in a substantial proportion of patients5 In our series, CD7+/ bined AML/ALL regimens during the induction as well as the CD2+ AML patients presented with a higher incidence of consolidation chemotherapy, with particular emphasis on the adenopathy and meningeal leukemia than did patients with “pure” prevention of meningeal leukemia, and, whenever possible, inAML, and were characterized by a poor response to chemotherapy in terms of complete remission (CR) achievement and d ~ r a t i o n . ~ cluded in a bone marrow transplantation program. Finally, further efforts should be addressed toward the classification of promiscuOn a clinical ground, our findings were closely in keeping with ous phenotypes on the basis of their clinical relevance. those reported by Cross et a1.3 Also, in the report by Pui et all CD7+/CD2+ AML was the most frequent hybrid pattern in 16 Ly+ AML cases. As in our series, most patients were classifiable as M1 FELICETTO FERRARA Division of Hematology according to the French-American-British classification, and in a LUIGI DEL VECCHIO consistent number of them a coexistence of large myeloid blasts Blood Transfusion Center and small blasts with hand-mirror morphology was found. Notwithstanding, Pui et all stated that “event free survival did not differ Cardarelli General Hospital between Ly+ AML patients and other AML patients.” What would Naples, Italy To the Editor: REFERENCES 1. Pui C-H, Raimondi SC, Head DR, Schell MJ, Rivera GK, Mirro J, Crist WM, Behm FG: Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse. Blood 78:1327, 1991 2. Drexler HG, Thiel E, Ludwig WD: Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. Leukemia 5:637, 1991 3. Cross AH, Goorha RM, Nuss R, Behm FG, Murphy SB, Kalwinsky DK, Raimondi SC, Kitchingman GR, Mirro J: Acute myeloid leukemia with T-lymphoid features: A distinct biologic and clinical entity. Blood 72579,1988 4. Ferrara F, Finizio 0, De Rosa C, Mele G, Mettivier V, Rametta V, Spada OA, Del Vecchio L Acute myeloid leukemia expressing T-cell antigens: Clinicohematological report on six cases. Leuk Lymphoma 3:217,1990 5. Del Vecchio L, Finizio 0, Lo Pardo C, Pane N, Schiavone EM, Vacca C, Ferrara F: Co-ordinate expression of T-cell antigens on acute myelogenous leukemia and of myeloid antigens on T-acute lymphoblastic leukemia. Speculation on a highly balanced bilinearity. Leukemia 5:815,1991 RESPONSE Ferrara and Del Vecchio’s findings are consistent with our observation that cases of acute myeloid leukemia expressing lymphoid-associated antigens (Ly+ AML) are characterized by French-American-British (FAB) M1 or M2 morphology, dual populations of large blasts with myeloperoxidase positivity and small blasts with hand-mirror morphology, and poorer response to myeloid-directed induction therapy.’ When analyses are limited to cases expressing CD7 and CD2, which comprised three-fourths of our Ly+ AML cases, these findings still hold true. However, our Ly+ AML cases, unlike those described by Ferrara and Del Vecchio, did not have a higher frequency of initial central nervous system (CNS) leukemia compared with other AML cases, and none developed CNS relapse. In our series, event-free survival did not differ between the Ly+ AML and other AML cases. Similarly, no difference was seen in analyses restricted to the CD7+/CD2+ subset (data not shown). Because of the small number of Ly+ AML cases expressing B-lineage-associated antigens, we cannot determine the clinical significance of these cases. However, there was no apparent difference in the presenting features and clinical outcome between the CD7+/CD2+ cases and those expressing B-lineage markers. In this regard, prednisone-vincristine-asparaginase therapy after failure on myeloid-directed therapy induced remission not only in the CD7+/CD2+ AML cases but also in one of the Ly+ cases expressing B-lineage-associated antigens. Although it is conceivable that the CD7+/CD2+ AML cases do represent a distinct From www.bloodjournal.org by guest on November 17, 2014. For personal use only. CORRESPONDENCE 2800 entity, we believe that further study is needed before these cases can be separated from other Ly+ cases. We are pleased that Ferrara and Del Vecchio concur regarding the need to include lymphoid-directed therapy in Ly+ AML. Whether bone marrow transplantation during first remission is indicated in these cases, in our opinion, will not be clear until intensive lymphoid- and myeloid-directed therapy has been tested. Such therapy, if effective, may alter the prognostic impact of lymphoid antigen expression in AML-as has been found for myeloid-associated antigen expression in childhood acute lymphoblastic leukemia.24 We concur with Ferrara and Del Vecchio that additional studies are needed to determine the clinical significance of “ectopic” antigen expression. We would reemphasize, however, that virtually all known “differentiation” surface antigens lack lineage specificity. CHING-HON PUI St Jude Children’sResearch Hospital The Universityof Tennessee,Memphis College of Medicine Memphis, TN REFERENCES 1. Pui C-H, Raimondi SC, Head DR, Schell MJ, Rivera GK, Mirro J Jr, Crist WM, Behm FG: Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse. Blood 78:1327, 1991 2. Pui C-H, Behm FG, Singh B, Rivera GK, Schell MJ, Roberts WM, Crist WM, Mirro J Jr: Myeloid-associated antigen expression lacks prognostic value in childhood acute lymphoblastic leukemia treated with intensive multiagent chemotherapy.Blood 75:198,1990 3. Pui C-H, Schell MJ, Raimondi SC, Head DR, Rivera GK, Crist WM, Behm FG: Myeloid-antigen expression in childhood acute lymphoblastic leukemia. N Engl J Med 325:1378, 1991 (letter) 4. Borowitz MJ, Shuster JJ, Land VJ, Steuber CP, Pullen DJ, Vietti TJ: Myeloid-antigen expression in childhood acute lymphoblastic leukemia. N Engl J Med 325:1379,1991 (letter)