Efficacy and toxicity of gemtuzumab ozogamicin in patients with acute myeloid leukemia

Gemtuzumab ozogamicin (GO) is a recently developed antibody-targeted chemotherapeutic agent and has been expected to be less toxic than conventional chemotherapy. We retrospectively evaluated the use of GO in 38 patients. Patients with acute myeloid leukemia (AML) at diagnosis and relapsed AML were treated with 6 and 9 mg/m(2) GO. Efficacy and toxicity of GO were analyzed, as well as several prognostic factors. A complete response (CR) was observed in 12 of 38 patients, including five patients with CR plus incomplete regeneration of platelets. In one patient a partial remission was observed. Twenty-five patients showed no change or progressive disease. The overall response (OR) in patients with AML at diagnosis was 47%, with the best response in patients with primary AML (OR 60%, compared with 21% OR in non-primary AML, P = 0.045). The OR in patients with relapsed AML was 22%. Median white blood cell (WBC) before treatment, CD33 expression on leukemic blasts, and kinetics of response were analyzed as prognostic factors. Median WBC was significantly lower in patients who responded to GO, compared with non-responders (2.1 x 10(9)/L vs. 6.8 x 10(9)/L, P = 0.036). CD33 expression and kinetics of response was not correlated to clinical outcome. Median days to reach 500 x 10(6)/L neutrophils and 100 x 10(9)/L platelets were 36 and 39 d, respectively. Infections and bleedings occurred in 45% and 12%, respectively. This report shows that GO has potent clinical activity and that the OR rate was by far the best in untreated primary AML patients.     

Adding low-dose gemtuzumab ozogamicin to fludarabine, Ara-C and idarubicin (MY-FLAI) may improve disease-free and overall survival in elderly patients with non-M3 acute myeloid leukaemia: results of a prospective, pilot, multi-centre trial and comparison with a historical cohort of patients

We report the final results of a prospective multi-centre trial testing the combination of chemotherapy (fludarabine, cytosine arabinoside and idarubicin; FLAI) followed by low-dose gemtuzumab ozogamicin (GO), for induction treatment of patients with CD33+ acute myeloid leukaemia (AML). Forty-six consecutive patients were treated: the median age was 66 (range: 60-80) years; the karyotype was unfavourable in 12 patients (26%), intermediate in 33 (71%) and favourable in one (3%). Eleven major infectious complications were recorded. There was one early death. Of the 45 evaluable patients, 24 achieved a complete response (CR; 52%), 66% and 33% in good-intermediate/poor karyotype patients. Median duration of CR was 7 (3-24) months. The cumulative incidence of relapse was 37% with an actuarial 2-year survival of 54%. These results were compared with 47 patients matched for age and karyotype who received FLAI, without GO. The proportion of patients achieving CR was comparable. However, patients with de novo AML receiving GO (n = 26) had a significantly lower risk of relapse at 2 years when compared with patients not receiving GO (n = 35) (40% vs. 80%, P = 0.01) and significantly better overall 2-year survival (40% vs. 14%P = 0.02). Patients with secondary AML had comparable outcome whether or not they received GO. This GO-based induction chemotherapy has a good toxicity profile. In keeping with a recent prospective randomised trial, the addition of GO seems to prolong disease-free survival.     

Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: the significance of the stem-cell glycoprotein CD34 (My 10)

A series of 23 monoclonal antibodies reactive with normal lymphoid and myeloid cells at various stages of differentiation were used to characterize 96 adult patients with acute myelocytic leukaemia (AML), concentrating on the possible role the expression of these antigens may have in predicting response to intensive chemotherapy. Only the expression of CD34 (P = 0.008) and HLA-DR (P = 0.035) was significant in predicting response to therapy; patients with leukaemic cells expressing CD34 (My10) had a complete remission (CR) rate of 59% compared to 87% for those with blasts not expressing the antigen. In a multivariate analysis predicting for CR, the expression of CD34, the disease category (de novo AML versus secondary AML [SAML] or a history of antecedent haematological disorder [AHD]), and WBC were significant covariates. Adjusting for disease category and WBC, patients with CD34-positive AML were one-third as likely to enter CR as with those with disease not expressing the antigen (P = 0.066). Comparison of clinical characteristics between the 58 patients whose leukaemia expressed CD34 and the 33 which were CD34-negative found that patients with CD34-positive AML had a higher incidence of SAML and AHD, a lower WBC at diagnosis, and a more frequent incidence of chromosomal abnormalities involving chromosomes 5 and/or 7. Twenty-eight of these patients also had immunophenotyping performed at relapse. Patients who presented with CD34-positive AML, and entered remission, and then relapsed all recurred with CD34-positive leukaemia; there was no case of CD34-positive AML at diagnosis relapsing with CD34-negative disease. In addition, there were patients presenting with CD34-negative AML and then relapsing with CD34-positive AML. These results suggest that intensive cytoreductive therapy is ineffective against CD34-positive AML. Patients who present with CD34-positive AML may require different therapeutic approaches to completely eradicate their disease.     

The role of gemtuzumab ozogamicin in acute leukaemia therapy

Gemtuzumab ozogamicin (GO) is an immunoconjugate that binds to CD33 on the surface of acute myeloid leukaemia (AML) blasts and, after internalisation, releases a cytotoxic drug, calicheamicin. GO is approved by the US Food and Drug Administration for the treatment of CD33-positive AML at first relapse in patients 60 years and older who are not candidates for other cytotoxic therapy. GO as a single agent has low antileukaemic activity. When given to patients meeting the criteria noted above, it produces a complete response (CR) rate of only 12%, with another 12% achieving CR with inadequate platelet recovery (CRp). The median survival of patients treated with GO monotherapy is 11.2 months. GO therapy at 9 mg/m(2) is complicated with hepatic veno-occlusive disease in 5-10% of patients, particularly prior to or following stem cell transplantation. GO at lower doses combined with chemotherapy as induction or postremission therapy is promising, however, and phase III trials are ongoing. GO is probably most active in acute promyelocytic leukaemia (APL). It is used for induction regimens in high-risk APL and for the elimination of minimal residual APL. Case reports suggest that GO also has activity in CD33-positive acute lymphoblastic leukaemia. In conclusion, single agent GO can induce responses in patients with CD33-positive AML in first recurrence. The future of GO is its use in combination with other cytotoxic agents. Ongoing clinical trials may better define the role of GO combinations, particularly in untreated AML.     

Poor response to intensive chemotherapy in de novo acute myeloid leukaemia with trilineage myelodysplasia

Summary. The findings of morphologically dysplastic features in haemopoietic cells in de novo acute myeloid leukaemia (AML) has been named AML with trilineage myelodysplasia (AML/TMDS). We analysed the clinical data, karyotypes, and treatment outcomes of 230 de novo AML patients treated with the Japan Adult Leukaemia Study Group AML-87 protocol. 40 (17%) patients had AML/TMDS. Platelet count was significantly higher ( F =0·006) and bone marrow blasts were fewer ( P =0·01) in the AML/TMDS group than in the AML without TMDS. Abnormal karyotype was shown in 12/30 patients (40%) analysed.
The complete remission (CR) rate for AML/TMDS was significantly lower than AML without TMDS (63% v 81%) ( P =0·01). The overall survival curves showed that the 40 patients with TMDS had a significantly worse survival than the 190 without TMDS ( P =0·0005). AML/TMDS also showed significantly worse disease-free survival (DFS) ( P =0·0001).
Multivariate analysis revealed that the absence of TMDS in AML was the most significant factor in obtaining CR ( P =0·01) and a significant factor in predicting longer DFS ( P =0·04). Our data suggest that AML/TMDS responds poorly to intensive chemotherapy. Further study is required to determine the best treatment strategy for AML/TMDS and the biological differences between AML/TMDS and other types of AML.     

Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation

CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multidrug resistance, but its clinical and prognostic significance has not been clearly identified. This study examined CD56 expression in 37 adult de novo AML patients with t(8:21). CD56 was expressed in 25 cases (67.6%). Complete remission (CR) rates were similar in both groups (91.7% vs. 88.7%; P = 0.73), but the relapse rates differed considerably (60% vs. 25%; P = 0.02). The median duration of disease-free survival (DFS) was significantly shorter in the CD56+ (median, 12.2 +/- 6.4 months) than in the CD56- group (median, not reached) (P = 0.02). In addition, the median duration of survival differed significantly in the CD56+ group (median, 14.9 +/- 4.4 months) compared with the CD56- group (median, not reached) (P = 0.01). Of the fifteen transplanted patients who achieved CR, allogeneic HST was performed from their siblings. The median duration of DFS in the CD56+ patients was significantly shorter than the CD56- patients (median, 24.4 +/- 4.5 months vs. median, not reached; P = 0.02). We concluded that CD56 expression correlates to a reduced DFS and survival for AML patients with t(8:21), including those patients who underwent transplantation.     

Gemtuzumab ozogamicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated on compassionate-use basis

Gemtuzumab ozogamicin (GO; Mylotarg) was developed to treat CD33(+) acute myeloid leukemia (AML). To date, only studies in adults and preliminary data from a phase 1 study in children have been reported. We report data on 15 children with relapsed/refractory CD33(+) AML who were treated with GO monotherapy on compassionate use basis (4-9 mg/m(2) up to 3 courses). Eight children showed a reduction in bone marrow blasts to 5% or less, including 5 in complete remission without full platelet recovery (CRp). Three of the 5 children with CRp received transplants almost directly following the last GO course, without awaiting further platelet regeneration. Hence in these children no clear discrimination between complete remission (CR) and CRp could be made. In 6 of 8 responding patients further treatment was given consisting of stem cell transplantation (SCT). Two patients are still alive, currently 6 and 9 months after SCT. Hematologic toxicity was difficult to assess due to subsequent SCT or leukemia. Side effects, in one patient each included veno-occlusive disease, transient grade 3 hyperbilirubinemia, transient grade 3 transaminase elevation, and grade 3 hypotension during GO administration. No infections or mucositis occurred. This report demonstrates clinical efficacy of GO in a subset of relapsed/refractory pediatric CD33(+) AML patients and suggests that intensive postremission therapy after remission induction by GO may result in durable responses in some patients, although follow-up is still short. Further studies are needed to determine the efficacy and safety of GO in children with AML.     

Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P- glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P- gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.     

Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine

The treatment of older patients with acute myeloid leukemia (AML) remains unsatisfactory, with complete remission (CR) achieved in only approximately 50% and long-term disease-free survival in 10% to 20%. Three hundred eighty-eight patients (60 years of age and older) with newly diagnosed de novo AML were randomly assigned to receive placebo (P) or granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM in a double-blind manner, beginning 1 day after the completion of 3 days of daunorubicin and 7 days of cytarabine therapy. No differences were found in the rates of leukemic regrowth, CR, or infectious complications in either arm. Of 205 patients who achieved CR, 169 were medically well and were randomized to receive cytarabine alone or a combination of cytarabine and mitoxantrone. With a median follow-up of 7.7 years, the median disease-free survival times were 11 months and 10 months for those randomized to cytarabine or cytarabine/mitoxantrone, respectively. Rates of relapse, excluding deaths in CR, were 77% for cytarabine and 82% for cytarabine/mitoxantrone. Induction randomization had no effect on leukemic relapse rate or remission duration in either postremission arm. Because cytarabine/mitoxantrone was more toxic and no more effective than cytarabine, it was concluded that this higher-dose therapy had no benefit in the postremission management of older patients with de novo AML. These results suggest the need to develop novel therapeutic strategies for these patients. (Blood. 2001;98:548-553)     

Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial

Risk assessment in acute myeloid leukemia (AML) using pretreatment characteristics may be improved by incorporating parameters of early response to therapy. In the 1992 trial of the German AML Cooperative Group (AMLCG), the amount of residual leukemic blasts in bone marrow was assessed one week after the first induction course (day 16 blasts). A total of 449 patients 16 to 76 years of age (median, 53 years) with de novo AML entered the trial and were evaluable. Treatment included TAD/HAM (thioguanine, cytosine arabinoside, and daunorubicin/high-dose cytosine arabinoside and mitoxantrone) double induction, TAD consolidation, and randomly either maintenance therapy or S-HAM consolidation. Cytogenetics were favorable, intermediate, unfavorable and not available in 10.0%, 48.3%, 13.1%, and 28.5%, respectively. Day 16 blasts ranged from 0% to 100% (median, 5%, mean +/- SD, 18.6 +/- 28.5%). Complete remission (CR) rate was 72.6%, 17.6% had persistent leukemia (PL), and 9.8% succumbed to hypoplastic death. Median overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were 18, 9, and 15 months with 28.4%, 21.6%, and 30.1% at 5 years, respectively. As a continuous variable, day 16 blasts were related to CR rate (P < 0.0001), PL rate (P < 0.0001), OS (P < 0.0001), EFS (P < 0.0001), and RFS (P = 0.0049). Multivariate analyses identified the following parameters to be associated with the respective end points. CR rate: day 16 blasts (P <.0001), age (P =.0036), and LDH (P =.0072); OS: unfavorable cytogenetics (P <.0001), day 16 blasts (P <.0001), age (P <.0001), and LDH (P =.0040); EFS: unfavorable cytogenetics (P <.0001), LDH (P <.0001), day 16 blasts (P <.0001), and age (P =.0061); RFS: unfavorable cytogenetics (P <.0001), LDH (P <.0001), and day 16 blasts (P =.0359). The prognostic significance of day 16 blasts is independent of pretherapeutic parameters and predicts outcome even in patients achieving a CR.     

早期分化抗原在急性白血病中的表达及其意义

目的　探讨CD3 4 、CD90 及CD13 3 在急性白血病 (AL)中的表达及其意义。方法　采用三色直接免疫荧光法测定 76例AL患者白血病细胞膜上CD3 4 、CD90 及CD13 3 抗原的表达 ,半定量RT PCR方法测定CD13 3 mRNA的表达。结果　 (1)AL患者的CD3 4 及CD13 3 表达高于正常对照组(46 37%、0 4 7% )、(2 1 93%、0 2 9% ) ,P值均 <0 0 1;但CD90 的表达二者间差异无统计学意义(0 5 1%、0 2 5 % ) ,P >0 0 5 ;AL、对照组的CD13 3 抗原表达均与CD13 3 mRNA表达相一致。 (2 )急性淋巴细胞白血病 (ALL)的CD90 阳性率高于急性髓细胞白血病 (AML) (P <0 0 5 ) ,B ALL的CD3 4 阳性率高于T ALL(P <0 0 5 )。AML中M4的CD13 3 阳性率最高 (P <0 0 1)。 (3)CD3 4 及CD13 3 阳性组AL的HLA DR阳性率显著高于阴性组 (79 1%、32 0 % ;82 8%、4 6 2 % ) ,P值均 <0 0 1;CD 3 4 AML的CD13 3 阳性率高于阴性组 (P <0 0 1) ,但两组之间CD90 阳性率差异无统计学意义。 (4)CD3 4 、CD90 及CD13 3 表达与AL的细胞或分子遗传学异常等临床预后因素无明显关系。 (5 )CD3 4 、CD90 及CD13 3 阳性组的完全缓解率及总反应率低于阴性组 ,但仅有CD3 4 /CD13 3 双阳性组完全缓解率低于双阴性组差异有统计学意义 (P <0 0 5 )。结论     

Combination of chemotherapy and gemtuzumab ozogamicin in adult Philadelphia positive acute lymphoblastic leukemia patient harboring CD33 expression

Gemtuzumab Ozogamicin (GO) is a humanized anti-CD33 antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin-g1. It was developed at the end of the nineties as 90% of the leukemic blast population of patients with acute myeloid leukaemia (AML) express the CD33 surface antigen (Dinndorf et al. [1] Blood 1986;67:1048-53). GO is currently approved in monotherapy for the treatment of CD33+ AML patients in first relapse, showing a 26% overall response rate and a median disease-free-survival of 5.2 months for responders (Larson et al. [2] Cancer 2005;104:1442-52). CD33 antigen expression is also observed at diagnosis (in 15% of cases) (Pui et al. [3] J Clin Oncol 1998;16:3768-73) or at relapse (Guglielmi et al. [4] Leukemia 1997; 11:1501-7) of acute lymphoblastic leukaemia (ALL), representing a potential cellular target for ALL patients. Case series have already demonstrated the efficacy of GO in children with relapsed CD33+ ALL with documentation of complete remission (CR) (Balduzzi et al. [5] Leukemia 2003;17:2247-8; Cotter et al. [6] Br J Haematol 2003;122:686-91; Zwaan et al. [7] Leukemia 2003;17:468-70). In the other hand, there is no report at our knowledge of the use of GO in the setting of adult CD33+ ALL patient. Here we report the case of a 30-year-old man with a refractory CD33+ ALL who received a salvage regimen combining chemotherapy + GO and achieved a transient CR.     

Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin

We report the results of a prospective, randomized phase 3 trial evaluating the use of gemtuzumab ozogamicin (GO) in an intensive consolidation approach in 657 patients 17-60 years of age. Patients in first complete remission (CR1) after cytarabine and standard- or high-dose daunorubicin induction received 2 cycles of consolidation with high-dose cytarabine followed by peripheral blood progenitor cell collection. The 352 patients who entered consolidation were randomized to receive GO (n = 132) or not (n = 138) and then proceeded to autologous hematopoietic cell transplantation (HCT). GO was given to 67 patients. Median follow-up was 50.9 months. Results of the intention-to-treat analysis demonstrated a 4-year disease-free survival (DFS) of 33.6% versus 35.9% (P = .54) and an overall survival (OS) of 41.3% versus 41.9% (P = .52) for those randomized to receive GO versus no GO, respectively. Patients with favorable- and intermediate-risk acute myeloid leukemia (AML) treated with high-dose daunorubicin and autologous HCT had 4-year DFS rates of 60% and 40% and OS rates of 80% and 49.3%, respectively. For younger AML patients in CR1, autologous HCT should be considered in favorable- and intermediate-cytogenetic risk patients who do not have an allogeneic donor. The addition of a single dose of GO in this setting did not improve outcomes.     

XIAP expression correlates with monocytic differentiation in adult de novo AML: impact on prognosis

Antiapoptotic proteins like the inhibitor of apoptosis proteins (IAPs) are molecular markers potentially useful for the characterization of acute myeloid leukemia (AML). We screened 92 adults with de novo AML for the protein expression of various IAPs, Bcl-2 family members and the proform of Caspase-3 using quantitative immunoblot and flow cytometry. XIAP expression correlated with myelomonocytic French-American-British (FAB) subtypes M4/M5 (P < 0.05) and expression of monocytic markers (CD 14, CD 36; P < 0.05; CD 4, HLA-DR; P < 0.01) in AML blasts. In addition, XIAP was overexpressed in normal monocytes but undetectable in granulocytes. In AML, XIAP expression was significantly lower in patients with favorable than intermediate or poor cytogenetics (n = 74; P < 0.05). In total, 62 of the examined patients were treated according to the German AML Cooperative Group (AMLCG) 92 protocol. These patients were analyzed for prognostic significance of apoptosis-related proteins. Patients expressing low levels of XIAP enjoyed better overall survival than patients expressing high amounts of XIAP (mean, 9 (n = 41) versus 19 months (n = 21); P < 0.05). Other IAPs, most importantly Survivin, were of no prognostic value. We conclude that XIAP but not other IAP family members is associated with monocytic differentiation in normal and malignant myelopoiesis, and may be of prognostic significance for overall survival in adult de novo AML.     

Acute myeloid leukemia with T-lymphoid features: a distinct biologic and clinical entity

We studied the clinical and biologic features of 10 cases of acute leukemia that met standard French-American-British (FAB) criteria for acute myeloid leukemia (AML) but in which the blast cells also expressed the T-cell-associated CD2 surface antigen. All cases had greater than 3% myeloperoxidase and Sudan black B-positive leukemic blasts, and blasts from seven cases contained Auer rods. Reactivity of the cells with a panel of monoclonal antibodies (MAbs) indicated that leukemic cells in all cases expressed myeloid-associated (CD11b, CD13) surface antigens, further supporting the diagnosis of AML. However, blasts from every patient coexpressed the T-cell-associated surface CD2 and CD7 as well as cytoplasmic CD3 antigens. Blasts from five patients expressed surface CD25, whereas blasts from only one expressed surface CD3. Five patients had rearranged T-cell receptor beta-chain genes, whereas only three had rearranged T-cell receptor gamma-chain genes. This pattern of lineage-related gene expression appears to define a distinct subtype of AML with T-lymphoid features (CD2+ AML) and could reflect either aberrant gene expression in leukemic blasts or transformation of a pluripotent stem cell having a flexible pattern of gene expression. Clinically, these 10 patients presented at an older age with a higher leukocyte count and a higher frequency of lymphadenopathy than did children whose blast cells were characteristic of myeloid leukemia. Patients with CD2+ AML also had poorer responses to remission induction therapy (50% v 80% entered complete remission, P = .05). However, each of the five children who failed induction chemotherapy on AML protocols had a striking response to drug combinations usually reserved for lymphoid leukemia. We conclude that this leukemia with mixed lymphoid and myeloid characteristics is a distinct biologic and clinical entity.     

Surface marker expression in acute myeloid leukaemia at first relapse

Surface markers were studied at first relapse in 66 cases of acute myeloid leukaemia (AML), using a panel of five monoclonal antibodies directed to CD13, CD14, CD15, CD33 and CD34 antigens. At time of relapse, there was increased expression of CD33 (P = 0.002) and CD34 (P = 0.0001), and decreased expression of CD13 (P = 0.004) and CD15 (P = 0.0001) antigens by comparison to initial diagnosis. There was no strict correlation with the FAB classification. However, CD13 and CD33 expression changes preferentially affected granulocytic leukaemias. At relapse, CD14 and CD34 were significantly more expressed in monocytic than in granulocytic AML (P = 0.01 and 0.003 respectively). In a multivariate analysis, CD34 expression was associated with a low CR rate (P = 0.001) and short survival (P = 0.05), whereas CD15 expression was associated with long survival (P = 0.0004). These results suggest that AML tends to relapse with a less differentiated phenotype than observed at diagnosis and that AML with less differentiated phenotype is of poor prognosis after first relapse, as also observed at diagnosis.     

The value of dot plot patterns and leukemia-associated phenotypes in AML diagnosis by multiparameter flow cytometry

The immunophenotypic features in patients with acute myeloid leukemia (AML) were investigated at diagnosis using a wide antibody panel including progenitor-associated, myeloid and lymphoid markers in quadruple combinations. Analyzed were bone marrow samples from 37 adult and pediatric patients for exact identification of AML blasts according their localization on CD45/SSC dot plots and aberrant immunophenotypes in various subtype of AML. We found the localization of AML blasts on CD45/SSC dot plots, which in combination with immunophenotype profile of blasts allow discrimination of several AML subtypes (M0-M2, M3, M4/M5 and other types). In 27/37 AML patients (73%) at least one leukemia-associated phenotype (LAP) was found, two or more aberrancies coexisted in more than a half of them (78%). Asynchronous expression was the most frequent type of LAP (77.8%, 21/27) followed by coexpression of lymphoid-associated antigens, which occurred in 18/27 (66.7%) patients. Presented study showed that leukemic cells of each AML patient had a unique antigenic profile and could be discriminated from their normal counterparts based on typical light scatter profiles and aberrant antigen expression that could further be used for detection of minimal residual disease.     

The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission

We report the results of a prospective, patient self-selected study evaluating whether haploidentical related donor stem cell transplantation (HRD-HSCT) is superior to chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Among totally 419 newly diagnosed AML patients, 132 patients with intermediate- and high-risk cytogenetics achieved CR1 and received chemotherapy alone (n = 74) or HSCT (n = 58) as postremission treatment. The cumulative incidence of relapse at 4 years was 37.5% ± 4.5%. Overall survival (OS) and disease-free survival (DFS) at 4 years were 64.5% ± 5.1% and 55.6% ± 5.0%, respectively. The cumulative incident of relapse for the HRD-HSCT group was significantly lower than that for the chemotherapy-alone group (12.0% ± 4.6% vs 57.8% ± 6.2%, respectively; P < .0001). HRD-HSCT resulted in superior survival compared with chemotherapy alone (4-year DFS, 73.1% ± 7.1% vs 44.2% ± 6.2%, respectively; P < .0001; 4-year OS, 77.5% ± 7.1% vs 54.7% ± 6.3%, respectively; P = .001). Multivariate analysis revealed postremission treatment (HRD-HSCT vs chemotherapy) and high WBC counts at diagnosis as independent risk factors affecting relapse, DFS, and OS. Our results suggest that HRD-HSCT is superior to chemotherapy alone as postremission treatment for AML.