Day 14 Bone Marrow Evaluation During Acute Myeloid Leukemia Induction in a Real-world Canadian Cohort

IntroductionThe 2017 National Comprehensive Cancer Network guidelines for acute myeloid leukemia have recommended performing bone marrow (BM) aspiration and BM trephine biopsy (BMTB) 14 to 21 days after starting induction therapy (commonly referred to as “day 14 [D14] marrow”). Those who do not achieve a hypoplastic marrow, with cellularity < 20% and blasts < 5%, are recommended to undergo 2-cycle induction (2CI). We performed a retrospective analysis to determine the impact of D14 BM characteristics in predicting for remission, association with overall survival (OS), and the effect of 2CI according to the D14 BM results.Patients and MethodsPatients aged 18 to 70 years undergoing induction therapy with standard “7 + 3” regimens were included. D14 cellularity was determined from BMTB samples and the blast percentage was assessed by morphology on BM aspiration and BMTB samples. The outcomes evaluated included the rates of complete remission (CR) and OS.ResultsA total of 486 patients with results from D14 BM evaluation were included in the present study. On multivariate analysis, cytogenetic risk and D14 blasts < 5% were predictive of CR/CR with incomplete count recovery (P < .001). Cytogenetic risk (P < .001), age < 60 years (P = .001), and D14 blasts < 5% (P = .045) predicted for OS. 2CI was performed in 131 patients (27%). Patients with hypocellular D14 BM but residual blasts (n = 106) underwent 2CI in 46% of cases, with improved remission rates (43.9% vs. 72.0%; P = .004) but no difference in OS.ConclusionsThe results from D14 BM evaluations are predictive of subsequent remission and OS. Our findings did not show a survival benefit with D14 BM-driven 2CI.     

Syngeneic hematopoietic stem cell transplantation for acute myeloid leukemia: a propensity score-matched analysis

The present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1.Subject terms: Acute myeloid leukaemia, Cancer immunotherapy     

Effect of Dose Ratio on Mitoxantrone and Daunorubicin in Acute Myeloid Leukemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

PurposeTo investigate the effects of mitoxantrone and daunorubicin in induced chemotherapy on complete remission (CR), death during induction therapy, overall survival (OS), disease-free survival (DFS), and relapse in patients of all ages with acute myeloid leukemia (AML).MethodsWe searched published reports at the Medline, Embase, and Cochrane Databases as well as other databases from inception through July 2019. There was no restriction on date of publication or language (PROSPERO registration CRD42018095843).ResultsWe enrolled 12 randomized controlled trials that included data of 4583 AML patients whose disease was untreated or relapsed/refractory, and compared the CR, death during induction therapy, DFS, and OS between mitoxantrone and daunorubicin. Mitoxantrone significantly increased the CR rate (relative risk = 1.07; 95% confidence interval [CI], 1.01, 1.14; P = .03) and DFS (hazard ratio = 0.87; 95% CI, 0.79, 0.96; P = .005) compared to daunorubicin. However, there was no significant difference in death during induction therapy (relative risk = 1.00; 95% CI, 0.81, 1.24; P = .99) and OS (hazard ratio = 0.94; 95% CI, 0.87, 1.01; P = .077) between the two drugs.ConclusionAlthough more studies are needed to compare mitoxantrone with higher-dose daunorubicin, the results showed that compared to daunorubicin, mitoxantrone can significantly improve CR and DFS in patients of all ages. These findings suggest that mitoxantrone may be a better choice than daunorubicin as an induction chemotherapy agent for AML patients, especially in developing countries.     

Prognostic significance of the Geriatric 8 score alone and included with genetic risk group in older adults with acute myeloid leukemia

IntroductionAs the numbers of older adult patients with acute myeloid leukemia (AML) continue to increase, the establishment of a simple geriatric assessment specifically for AML represents an unmet need. This study aimed to assess the impact of the Geriatric 8 (G8) score on overall survival (OS).Materials and MethodsWe retrospectively analyzed 100 patients ≥60 years old with newly diagnosed AML.ResultsMultivariate Cox modeling identified G8 score as a significant prognostic factor for OS (hazard ratio 0.891, 95% confidence interval [CI] 0.808–0.983). A linear association between G8 score and mortality risk was confirmed in a Cox model with restricted cubic spline. Multivariate receiver operating characteristic curves demonstrated a significant improvement in prediction ability when G8 score was added to cytogenetic risk group. The combination of G8 score and cytogenetic risk group yielded a significant continuous net reclassification improvement (0.718; 95%CI 0.353–1.082; P < 0.001). Decision curve analysis showed a clinical net benefit associated with adding G8 score to cytogenetic risk group.DiscussionG8 score not only offered a strong prognostic factor for OS, but also markedly improved prediction accuracy for mortality when incorporated with cytogenetic risk group.     

Characteristics and Outcomes of Secondary Acute Myeloid Leukemia and Acute Myeloid Leukemia With Myelodysplasia-Related Changes: Multicenter Study From the Thai Acute Leukemia Study Group

BackgroundSecondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) both result in dismal outcomes. This retrospective study aimed to determine whether these features are poor prognostic factors independent of older age and adverse cytogenetics, which are commonly associated with a poor prognosis.MethodsThe characteristics and real-world outcomes of sAML and AML-MRC from the Thai AML registry database were investigated.ResultsFrom a total of 992 newly diagnosed AML patients, 315 (31.8%) patients were classified into sAML or AML-MRC subtypes. Older age, low white blood cell (WBC) count, low bone marrow blast, and adverse cytogenetic risk were commonly present in sAML and AML-MRC compared to de novo AML. Complete remission after 7 + 3 induction therapy occurred in 42.3% of patients with sAML or AML-MRC and 62.4% of de novo AML (P < .001). The median overall survival (OS) of sAML, AML-MRC, and de novo AML were 6.9, 7.0, and 12.2 months, respectively (P < .001). The independent prognostic factors for inferior OS were older age, intermediate-risk or adverse-risk cytogenetics, WBC count > 100 × 10⁹/L, poor performance status, and a subgroup of AML-MRC with the morphologic criteria of multilineage dysplasia (AML-MRC-M). In addition, sAML, AML-MRC, and a WBC count > 100 × 10⁹/L were pre-treatment prognostic factors associated with poor relapse-free survival (P = .006, P = .017, and P < .001, respectively).ConclusionBoth sAML and AML-MRC are independently associated with poor outcomes in Thai patients. Our study supports AML-MRC-M as an adverse prognostic factor for OS.     

Allogeneic Stem Cell Transplantation in Patients With FLT3-ITD Mutated AML: Transplantation in CR1 Is the Decisive Factor for Good Outcome

BackgroundPatients with internal tandem duplication in fms-related tyrosine kinase receptor gene 3 (FLT3-ITD)-mutated acute myeloid leukemia (AML) have a dismal prognosis and the only curative option seems to be allogeneic stem cell transplantation (alloSCT). However, its timing is still matter of debate.Patients and MethodsWe retrospectively analyzed 73 consecutive AML patients with FLT3-ITD (median age 53, range 20-68 years) allografted with consistent policy to try to refer them all for upfront alloSCT in first complete remission (CR1).ResultsWith a median follow-up of 44 (range, 5-135) months the 5-year overall survival (OS)/disease-free survival (DFS) probabilities were 49%/47%. The cumulative incidence of relapse and nonrelapse mortality (NRM) were 37% and 14%, respectively. The estimated 5-year OS for patients who received transplantation in CR1 was 62% versus 0% for patients who received transplantation beyond CR1. Multivariable analysis identified stem cell transplantation beyond CR1 as the key factor for poor OS (hazard ratio [HR], 5.41; P < .0001), DFS (HR, 4.41; P = .0002), and high relapse incidence (HR, 8.08; P < .0001). Acute graft versus host disease Grade ≥3 predicted higher NRM (HR, 3.80; P = .059) as well as inferior OS (HR, 2.04; P = .0079). No association of patient age, nucleophosmin status, donor type, conditioning, and other variables on the survival was detected.ConclusionAlloSCT should be regarded with urgency as soon as CR1 is achieved in this subset of AML patients.     

Long-Term Results in Multiple Myeloma After High-Dose Melphalan and Autologous Transplantation According to Response Categories in the Era of Old Drugs

BackgroundThe aim of this study was to investigate the correlation between the long-term prognosis of multiple myeloma (MM) and the quality of response to therapy in a cohort of 173 patients treated with high-dose melphalan (HDM) and autologous transplantation in the era of old drugs.Patients and MethodsA total of 173 patients with de novo MM who received a transplant between 1994 and 2010 were analyzed. VAD (vincristine, doxorubicin [Adriamycin], dexamethasone) was used as front-line regimen before auto-HPCT. The conditioning was HDM 200 mg/m². Patients were evaluated for clinical response using the criteria from the European Group for Blood and Marrow Transplantation, modified to include near complete remission (nCR) and very good partial remission (VGPR).ResultsThe response distribution after transplantation in our series was complete remission (CR) in 33 cases (19%), nearly complete remission (nCR) in 38 cases (22%), VGPR in 30 cases (17%), partial remission (PR) in 65 cases (38%), and stable disease (SD) in 7 cases (4%). Patients were followed for 48 ± 36 months. Median overall survival (OS) was not reached for the CR group. Progression-free survival (PFS) was 122 months for CR, 55 months for nCR, 56 months for VGPR, 32 months for PR, and 22 months for SD. Significant differences in PFS and OS were found between the CR and nCR groups (P = .003 and P = .001, respectively), between the CR and VGPR groups (P = .002 and P = .001, respectively), and between the CR and PR groups (P = .000 and P = .001, respectively). Responses were clustered in 3 main categories, ie, CR, nCR + VGPR + PR, and SD. The respective 10-year PFS and OS values were 58% and 70% for CR, 15% and 18% for nCR + VGPR + PR, and 0% and 0% for SD.ConclusionThe achievement of depth and prolonged response represents the most important prognostic factor. The relapse rate is low for patients in CR after 10 years of follow-up, possibly signifying a cure.     

Primary plasma cell leukemia: a retrospective multicenter study of 73 patients

BackgroundEpidemiological and clinical information on primary plasma cell leukemia (pPCL) are rarely reported. The aims are to evaluate the clinical features, prognostic factors, and efficacy of treatments in pPCL.Patients and methodsA multicenter retrospective cohort study was carried out from January 2000 to December 2008 in 26 Italian hematology divisions. A total of 128 cases of plasma cell leukemia were collected, and 73 of them (57%) were classified as primary (male/female 43/30).ResultsSixty-four patients had at least 1 sign of end-organ damage and 10 had extramedullary localization. One patient died early; of the remaining patients, 36 (50%) received anthracycline-based regimens as first-line therapy, 17 (24%) single alkylating agents, and 30 (42%) bortezomib or thalidomide as additional (n = 11) or unique treatments (n = 19). Twenty-three patients (31%) underwent autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT). The median overall survival (OS) was 12.6 months; complete or partial response was achieved in 22 (30%) and 18 patients (25%), respectively; the median duration of response (DOR) was 16.4 months. HSCT patients had a longer OS and DOR (median 38.1 and 25.8 months, respectively) compared with nontransplanted patients (9.1 and 7.3 months, respectively, P < 0.001). OS was influenced by nonresponse to treatment, hypoalbuminemia, and HSCT. DOR was favorably influenced only by HSCT.ConclusionspPCL is an aggressive disease with a poor prognosis and a low response rate to conventional therapy. HSCT is effective, increasing OS and DOR by 69% and 88%, respectively. The use of bortezomib and thalidomide may improve outcomes.     

Outcome of CD20-positive Adult B-cell Acute Lymphoblastic Leukemia and the Impact of Rituximab Therapy

BackgroundIn adult B cell precursor acute lymphoblastic leukemia (BCP-ALL), CD20 expression has generally been associated with an adverse prognosis. Incorporating rituximab to standard of care is found to improve the outcome of CD20⁺ BCP-ALL. The aim of this study is to estimate the prognostic effect of CD20 expression and the impact of rituximab in BCP-ALL in Saudi Arabia.Patients and MethodsWe performed a retrospective study of 55 Saudi adult patients with BCP-ALL in King Fahad Specialist Hospital in Dammam from 2008 to 2017.ResultsThe proportion of CD20⁺ cases was approximately 55%. Excluding rituximab-treated patients, the 5-year overall survival (OS) rate of CD20⁺ patients was lower than CD20⁻ patients (56% vs. 66%; P = .62). Among CD20⁺ patients, the proportion that received rituximab was approximately 27%. Comparing CD20⁺ patients with and without rituximab, all patients who received rituximab achieved complete remission (CR) 4 weeks post-induction. The 3-year OS rate (88% vs. 63%; P = .35) and the 2-year event-free survival rate (70% vs. 68%; P = .75) were in favor of rituximab. In univariate and multivariate analyses, CR 4 weeks post-induction is recognized as an independent predictor of outcome. However, differences in survival rates did not have a statistical significance.ConclusionCD20 expression in adult patients with BCP-ALL seems to be higher in Saudi Arabians than in Caucasians, and it seems to have a tendency towards an inferior outcome in terms of OS. Incorporating rituximab to standard of care seems to improve the outcome in terms of CR, OS, and event-free survival.     

AML in Saudi Arabia: Analysis According to the European LeukaemiaNet 2017 Cytogenetic Classification

IntroductionTo the best of our knowledge, few studies have addressed the prognosis of patients with acute myeloid leukemia (AML) in Saudi Arabia. The present study retrospectively analyzed the prognostic factors in patients with de novo AML at a single institution owing to the observation of some differences with the reported data from the Western world.Patients and MethodsPatients with de novo AML who had been referred to King Abdulla Medical City were included. All patients had undergone bone marrow aspiration, biopsy, flow cytometry, cytogenetics (conventional and fluorescence in situ hybridization panel performed at Mayo Clinic), molecular tests, and other routine tests.ResultsThe data from 170 patients were reviewed. Of the 170 patients, 26 had had acute promyelocytic leukemia, 16 with AML had received less intensive therapy, 119 had received intensive induction, and 8 had refused treatment. The present analysis was limited to the 119 patients who had received intensive induction therapy. For the major cytogenetic categories, 17 of 27 patients with core binding factor leukemia (62.9%) were reassigned to the intermediate (n = 10; 37%) or unfavorable (n = 7; 25.9%) risk group according to the FLT3-ITD and NPM results. Of the 50 cases of normal cytogenetic findings, 2 (4%) were considered unfavorable, 12 (24%), favorable, 30 intermediate (60%), and 6 (12%) unknown. The median leukemia-free survival was 21.5 months. The median overall survival was 16.4 ± 2.2 months, with a 3-year survival rate of 37.2%. Multivariate Cox regression analysis revealed that the cytogenetics results (P = .002) and the presence of FLT-3 (P = .03) were independent prognostic factors for relapse-free survival. Performance status, response, relapse, and cytogenetics findings were independent prognostic factors for survival.ConclusionsThe results from the present study revealed some differences in patient age and cytogenetic risk groups for patients with AML in our region and those in the Western world, including a younger median age, relevance of core binding factor leukemia, and a greater incidence of monosomies.     

Measurable Residual Disease Assessment and Allogeneic Transplantation as Consolidation Therapy in Adult Acute Lymphoblastic Leukemia in Colombia

IntroductionDetectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. The objective of the study was to assess disease-free survival (DFS) and overall survival (OS) of patients with ALL according with MRD status at the end of induction therapy in a Colombian population.Patients and MethodsWe assessed a retrospective cohort to compare DFS and OS in adults with de novo ALL according to MRD status at the end of induction chemotherapy, and the type of postinduction consolidation strategy used.ResultsA total of 165 adults with ALL were included in the MRD part of the study, 73 patients in the MRD-negative group and 92 in the MRD-positive group. Median DFS for the MRD-positive group was 11 months (95% confidence interval, 11.7-22.2) and was not reached for the MRD-negative group (P < .001). At 3 years, DFS was 18% and 55%, respectively (P < .001). The median OS for MRD-positive patients was 16 months (95% confidence interval, 8.8-23.15) and was not reached in the MRD-negative group. At 3 years, OS was 26% and 51% for the former and latter group, respectively. Among subjects who did not receive a transplant, median DFS was 21 months for MRD-negative patients and 9 months for MRD-positive patients (P < .001). The median DFS was not reached in either group, whereas 3-year DFS was 64% for MRD-negative and 70% for MRD-positive patients who underwent transplantation in first remission (P = .861).ConclusionMRD status at the end of induction is an independent prognostic factor for DFS and OS in adult ALL. Allogeneic transplantation in first remission could overcome the adverse prognostic impact of MRD.     

High Red Cell Distribution Width is an Adverse Predictive and Prognostic Factor in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemoimmunotherapy

IntroductionThe red blood cell distribution width (RDW) is an easy-to-obtain laboratory value that has emerged as a potential prognostic factor in solid and hematologic malignancies.Patients and MethodsWe evaluated 121 patients with de novo diffuse large B-cell lymphoma (DLBCL) treated with standard chemoimmunotherapy at our institution between 2010 and 2012. We categorized patients with high RDW (> 14.6%) and normal RDW (11.6%-14.6%). We fitted multivariate regression models for complete response (CR) and overall survival (OS).ResultsPatients with high RDW were less likely to achieve CR to chemoimmunotherapy than patients with normal RDW (48% vs. 83%; P < .001). The 5-year OS rate for patients with high RDW was lower than in patients with normal RDW (51% vs. 79%; P = .001). In multivariate regression models, high RDW was independently associated with lower odds of achieving CR (odds ratio, 0.32; 95% confidence interval [CI], 0.12-0.83; P = .02) and with higher risk of death from any cause (hazard ratio [HR], 2.04; 95% CI, 1.03-4.02; P = .04) than normal RDW in patients with DLBCL treated with chemoimmunotherapy. High RDW remained an independent adverse factor for OS after adjustment for the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index scores with HR 2.20 (95% CI, 1.12-4.31; P = .02) and HR 2.67 (95% CI 1.28-5.59; P = .009), respectively.ConclusionHigh RDW appears to be an adverse predictive and prognostic factor in patients with de novo DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).     

Chronic Lymphocytic Leukemia Patients With Deletion 11q Have a Short Time to Requirement of First-Line Therapy,But Long Overall Survival: Results of a Population-Based Cohort in British Columbia,Canada

BackgroundChronic lymphocytic leukemia (CLL) patients with 11q22.3 deletion (11q-) have an aggressive clinical course, and thus selection of first-line therapy in this group is important. This study aimed to improve our understanding of real-world practice patterns and outcomes of CLL patients with 11q- in a population-based setting.Patients and MethodsThe British Columbia CLL Database was used to identify patients with 11q-. Overall survival (OS) and treatment-free survival (TFS) were assessed after adjustment for prognostic factors.ResultsOf 1044 patients in the database, 125 had 11q- (12%). Sixty-nine patients had 11q- identified before therapy initiation and had a median OS and TFS of 14.7 (95% confidence interval [CI], 11.3-18.1) and 2.5 (95% CI, 1.5-3.6) years. Patient with copresence of 11q- and deletion 17p had a markedly worse prognosis, with median OS of 4.9 versus 14.7 years (P < .001). Most treated patients (33 of 52) received fludarabine with or without rituximab (FR). Patients treated with FR had a median OS of 12.8 years (standard error, 1.0), which was not statistically different from those treated with alkylator-containing therapy (P = .35).ConclusionAlthough median TFS of 11q- patients in this cohort was short at 2.5 years, OS remains long at 14.7 years, even when most patients received initial treatment without alkylators.     

Incidence and Prognostic Significance of High-Risk Cytogenetically Abnormalities in Multiple Myeloma Patients in Colombia

IntroductionMultiple Myeloma (MM) is the second most common hematological cancer, several cytogenetics abnormalities such as t(4;14), del (17p), and t(14;16) were identified as a high-risk for survival, in Latin America, we have very little data on cytogenetic alterations in MM. This study describes the incidence of high-risk cytogenetically abnormalities in a Colombian population and prognostic significance.MethodsIn a retrospective cohort of new diagnostic Multiple Myeloma between 2016 and 2020, we identified a high-risk cytogenetically abnormalities t(4;14), t(14;16), and 17p deletions by FISH techniques and described incidence. We followed patients until progression or death and comparing progression free survival (PFS) and overall survival (OS), according with high- risk cytogenetically features.ResultsWe included 135 newly diagnosed MM patients, the incidence of high-risk cytogenetically abnormalities were 30.3%, with 17.1% of 17p deletions, 14.1% of t(4;14) and 2.25% of t(14;16). According to the high risk cytogenetically abnormalities, the median PFS for the group of no abnormalities were 50.2 months 95% CI [25.2-62.4] and for the group of high-risk cytogenetic abnormalities 33.9 months 95% CI [23.6-NA] (P = .2). For OS the median were 76.9 months, 95% CI [67.5-NA] and 42.7 months 95% CI [33.3-NA], respectively (P = .009).ConclusionHigh-risk cytogenetically abnormalities were independent risk factor for OS but not PFS in this cohort of patients, and the incidence of del (17p) was slightly higher than the literature reports. MicroabstractPrognostic significance of high-risk cytogenetic abnormalities in Multiple Myeloma in Colombia is unknown. In a retrospective cohort study of 135 newly, diagnostic Multiple Myeloma we found incidence of high-risk cytogenetic abnormalities was 30.3%. The hazard ratio (HR) for disease progression or death compared high-risk cytogenetic group vs. control was 1.22, (95% CI, 0.73-2.05) (P = .2), and The HR for death for the group of high-risk cytogenetic abnormalities was 2.17, (95% CI, 1.19-3.97). In the group of high-risk cytogenetic abnormalities, if the patient received VRD as induction treatment the median PFS were 41.2 months 95% CI [13.3-NA] and 33.9 months 95% CI [24.9-NA] for patients with different induction treatment (P = .56)     

Interest of cytogenetic and FISH evaluation for prognosis evaluation in 198 patients with acute myeloid leukemia in first complete remission in a single institution

The prognostic interest of cytogenetic remission and fluorescent in situ hybridization (FISH) evaluation in patients with abnormal karyotype acute myeloid leukemia (AML) has been poorly studied. Among 198 patients that reached complete remission (CR), 24 did not reach cytogenetic remission (CyCR). CyCR had no prognosis impact, especially in patients with intermediate or unfavorable cytogenetic. Twenty of 52 evaluated patients in CyCR did not reach FISH CR. FISH CR was associated with better OS (p = 0.004) and tended to be associated with better disease-free survival (DFS) (p = 0.08). FISH evaluation may be a useful tool for prognosis evaluation and minimal residual disease (MRD) assessment in patients with abnormal cytogenetic AML.     

Allogeneic Hematopoietic Stem-Cell Transplantation Improves Disease-Free Survival Compared to Pediatric-Inspired Berlin-Frankfurt-Münster Chemotherapy in Adult Acute Lymphoblastic Leukemia

IntroductionAcute lymphoblastic leukemia (ALL) is a malign disease with poor prognosis in adults. After remission is achieved by induction therapy, administration of allogeneic hematopoietic stem-cell transplantation (AHSCT) is one of the standard treatment in adult ALL patients. Pediatric-inspired chemotherapy has been demonstrated to improve outcomes of adult ALL. The aim of this study was to compare the Berlin-Frankfurt-Münster-95 chemotherapy (BFM-95) regimen and AHSCT results in ALL patients with first complete remission.Patients and MethodsForty-seven patients who received the BFM-95 regimen and 83 patients who underwent AHSCT were compared. Primary endpoints were comparison of overall survival (OS) and disease-free survival (DFS) between groups.ResultsThere was no significant difference between the groups in terms of age, gender, or performance status. In BFM-95 and AHSCT, relapsed disease occurred in 11 (23.4%) and 24 (28.9%), respectively; the respective values for treatment-related mortality were 6 (12.7%) and 10 (12%) (P = .32 and .91). Five-year DFS was 38% with BFM-95 and 57% with AHSCT (P = .014). There was no 5-year OS difference in both groups (64% vs 60%, P = .13). While leukocyte count < 30 × 10⁹/L at the time of diagnosis (hazard ratio, 2.7; P = .021) and prophylaxis of central nervous system (hazard ratio, 2; P = .036) were prognostic for OS, the only factor that had a prognostic effect on DFS was AHSCT (hazard ratio, 1.6; P = .041).ConclusionAHSCT currently offers no special OS advantage but increases DFS compared to the BFM-95 regimen. AHSCT may be considered at first complete remission in patients at low risk of transplant-related mortality.     

Day +100 Platelet Count Predicts Survival After Allogeneic Hematopoietic Stem-Cell Transplantation in Children With Hematologic Malignancies

IntroductionRecovery of platelet count by day 100 after hematopoietic stem-cell transplantation (HSCT) is affected by many factors and has been reported to be a predictor of overall survival (OS) in a variety of diseases and donor types. We investigated the correlation between day +100 platelet count and OS after allogeneic HSCT in a relatively homogeneous cohort of pediatric patients with hematologic malignancies.Patients and MethodsWe conducted a retrospective study of 152 consecutive patients who underwent allogeneic HSCT at the Children’s Cancer Hospital Egypt between 2009 and 2015 with a minimum follow-up duration of 1 year after transplantation. All eligible patients received myeloablative conditioning, and all had matched related donors. Patients who survived without relapse until day 100 after HSCT were divided into 2 groups: early platelet recovery (EPR; platelet count ≥ 100 × 10⁹/L at day +100 after transplantation) and delayed platelet recovery (DPR; platelet count < 100 × 10⁹/L at day +100 after transplantation).ResultsAt day +100, 113 patients (74%) had EPR and 39 patients (26%) had DPR. With a median follow-up of 41 months (range, 12-93 months), 41 patients (27.2%) died, 35 of relapsed disease. The 3-year disease-free survival (DFS) and OS were 68 ± 7.84% and 71.9 ± 7.84%, respectively. The 3-year OS was 77.9% in the EPR group and 57.1% in the DPR group (P = .006). Three-year DFS of the EPR and DPR groups were 73.2 ± 9% and 54.8 ± 16.3%, respectively (P = .02). Incidence of disease relapse for EPR and DPR patients was 22.6% and 39.5%, respectively (P = .04). Multivariate analysis for survival identified DPR as a predictor of decreased survival (P = .002).ConclusionPatients with a robust platelet count at day 100 are likely to do well. However, patients who do not experience a platelet count of ≥ 100 × 10⁹/L have inferior long-term OS and DFS and may require further evaluation at the day 100 time point.     

Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: A retrospective analysis of JALSG‐APL97

For patients with relapsed acute promyelocytic leukemia (APL), all‐trans retinoic acid‐based salvage regimens can achieve second complete remission (CR2), but the optimal post‐remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation (HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)‐HSCT, 21 received allogeneic (allo)‐HSCT, and 30 received various regimens other than HSCT. The 5‐year event‐free survival (EFS) rate, overall survival (OS) rate and cumulative incidence of relapse (CIR) were 50.7%, 77.4% and 51.0% in the non‐HSCT group, 41.7%, 83.3% and 58.3% in the auto‐HSCT group and 71.1%, 76.2% and 9.8% in the allo‐HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo‐HSCT group than in other groups. Allo‐HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation‐related mortality (19%). Among older patients (age ≥40 years), the 5‐year OS was significantly better in the non‐HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2.     

Anthracycline-Induced Cardiotoxicity in Acute Myeloid Leukemia Patients Who Undergo Allogeneic Hematopoietic Stem Cell Transplantation

IntroductionThere is paucity of data regarding the cardiotoxic effects of anthracycline treatment in the context of acute myeloid leukemia (AML) patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT). Even a transient decrease in cardiac function might affect transplantation outcome.Patients and MethodsWe reviewed the clinical records and echocardiography examinations of 78 patients with AML who received induction therapy and underwent HSCT.ResultsTwenty-two patients (28%) received daunorubicin at a dose of 90 mg/m² per day and 53 patients (68%) received 60 mg/m² per day or an equivalent dose of idarubicin. In 14 patients (18%) the postinduction ejection fraction declined by at least 10%. This change was temporary in 6 patients and longstanding in the remainder. Patients who developed systolic dysfunction had inferior overall survival (13 months compared with 27 months; P = .013). Patients whose diastolic function deteriorated had improved survival outcome (38 months compared with 17 months; P = .048).ConclusionAlthough even transient reduction in systolic function might compromise survival outcome, diastolic dysfunction predicts improved survival in patients with AML who undergo HSCT.