Allogeneic Stem Cell Transplantation (allo-SCT) for Secondary Acute Myeloid Leukemia (AML) Following Breast Carcinoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3305-3305
Author(s):  
Sameh Ayari ◽  
Mohamad Mohty ◽  
Karin Bilger ◽  
Gaelle Guillerm ◽  
Denis Guyotat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Breast Carcinoma ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Increased Risk ◽  
Acute Myeloid

Abstract Abstract 3305 Poster Board III-193 Patients with breast carcinoma who received Radio and/or chemotherapy, have an increased risk for developing therapy-related myelodysplastic syndromes/acute myeloid leukemia (1-5%). Such secondary AMLs have often poor prognosis when treated with conventional chemotherapy. This retrospective series assessed the outcome of 29 female patients who were reported to the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire Registry, and who were treated with allo-SCT for secondary MDS/AML developing after initial therapy for breast cancer. The median age of patients at time of breast cancer treatment was 51 (range, 31-62) years. The median age at time of allo-SCT was 53 (range 31-63) years. Diagnosis included 21 AML and 8 MDS. Cytogenetics: four patients had CBF abnormalities, 10 had 11q23 abnormalities, 5 had an intermediate caryotype and 3 had unfavourable one. At time of allo-SCT, 21 patients were in complete remission (CR), while 8 had a refractory/relapsed disease. PBSCs were used as stem cell source in 18 patients, while 9 patients received classical bone marrow and one patient received an unrelated umbilical cord blood. Patients received a median of 5.2 ×10e6/Kg CD34+ cells. A matched related donor was used in 23 cases (82%) and an unrelated donor in 5 cases (18%). Conditioning regimen was myeloablative (Cy-TBI or Bu-Cy) in 7 cases (24%) and reduced-intensity in 22 cases (76%). Twenty four patients engrafted with a median time of 18 (range, 9-32) days for ANC>500/μL. Seven (24%) patients experienced grade 2-4 acute GVHD. Also, 7 patients (24%) experienced chronic GVHD (5 extensive and 2 limited). With a median follow-up of 24 (range, 3-129) months, 16 patients (55%) were still alive. Disease progression accounted for 6 deaths while transplant related causes (infection n=4, GVHD n=1, MOF n=1, cardiac failure n=1) occurred in 7 cases. The Kaplan-Meier estimates of overall and disease-free survival at 2 years were at 54 and 38% respectively. These results highlight the poor outcome of secondary leukemia occurring after therapy for breast cancer, even with the use of allo-SCT. Innovative maintenance approaches such as early use of hypomethylating or immunomodulatory agents after allo-SCT aiming to decrease the relapse are warranted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Haploidentical Stem Cell Transplantation for Acute Myeloid Leukemia: Current Therapies, Challenges and Future Prospective

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying-Jun Chang ◽  
Xiang-Yu Zhao ◽  
Xiao-Jun Huang
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Haploidentical Stem Cell Transplantation ◽  
Acute Myeloid

Haploidentical stem cell transplantation (haplo-SCT), an alternative donor source, offers a curative therapy for patients with acute myeloid leukemia (AML) who are transplant candidates. Advances in transplantation techniques, such as donor selection, conditioning regimen modification, and graft-versus-host disease prophylaxis, have successfully improved the outcomes of AML patients receiving haplo-SCT and extended the haploidentical transplant indictions for AML. Presently, treating de novo AML, secondary AML, therapy-related AML and refractory and relapsed AML with haplo-SCT can achieve comparable outcomes to those of human leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT), unrelated donor transplantation or umbilical cord blood transplantation. For some subgroups of AML subjects, such as patients with positive pretransplantation minimal/measurable residual disease, recent studies suggest that haplo-SCT might be superior to MSDT in decreasing relapse and improving survival. Unfortunately, for patients with AML after haplo-SCT, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes. In this review, we discuss the recent advances and challenges in haplo-SCT for AML treatment, mainly focusing on unmanipulated haplo-SCT protocols. We provide an outlook on future prospects and suggest that relapse prophylaxis, intervention, and treatment, as well as infection prevention and therapy, are areas of active research in AML patients who receive haploidentical allografts.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation Offers Similar Outcome after Myeloablative and Sequential Conditioning Regimen in Patients with Primary Refractory or Relapsed Acute Myeloid Leukemia: A Study from the Societe Francaise De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4367-4367
Author(s):  
Justine Decroocq ◽  
Raphael Itzykson ◽  
Stéphane Vigouroux ◽  
Mauricette Michallet ◽  
Ibrahim Yakoub-Agha ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Categorical Variables ◽  
Unrelated Donor ◽  
Acute Myeloid

Abstract Introduction: Acute myeloid leukemia (AML) patients failing to achieve complete remission or relapsing after intensive chemotherapy, have a dismal prognosis. In this setting, allogeneic hematopoietic cell transplantation (HCT) is a curative salvage therapy, but myeloablative conditioning (MAC) transplants are usually associated with high non-relapse mortality (NRM). Promising results have been reported using a sequential treatment approach (SEQ) consisting of cytoreductive chemotherapy, followed by reduced-intensity conditioning (RIC) and prophylactic transfusion of donor lymphocytes. Nevertheless, for young patients with refractory or relapsed AML, there is no definitive evidence to prefer SEQ rather than MAC HCT. The aim of this study, analysing the data from the SFGM-TC, was to compare the results of these two approaches in patients transplanted in AML not in complete remission. Methods: Inclusion criteria: a) HCT performed from January 2006 to December 2013 b) Patient age up to 50 years (y), c) Transplant for refractory or relapsed AML, c) SEQ or MAC regimen d) Matched sibling donor, matched or mismatched unrelated donor. PatientsÕ characteristics: 108 patients (median age: 38 y (range 1-50)) were analysed. Eighty-eight percent of patients were diagnosed with de novo AML and 12% with secondary AML. At diagnosis, 4% of patients were classified favorable, 33% Intermediate-1, 25% intermediate-2, and 38% adverse, according to the European LeukemiaNet (ELN) score. Before transplant, patients received a median of 2 lines of chemotherapy (range 0-3). At transplant, 53% of patients were in primary induction failure (PIF), 43% in relapse, and 4% were never treated and the median of bone marrow (BM) and circulating blast percentages were 19% (range 0-96) and 2% (range 0-93) respectively. Transplant modalities: 60 patients received a SEQ approach (cytoreductive chemotherapy with FLAMSA (N=40) or with clofarabine (N=20) + high-dose cytarabine, followed by RIC combining cyclophosphamide (CY) with 4 Gy total body irradiation (TBI) or with busulfan (BU)) while 48 patients received a MAC regimen (CY combined with 10-12 Gy TBI (N=20) or with BU (N=28)). Forty-one percent of patients were transplanted from a sibling and 59% from an unrelated donor. Stem cell source was peripheral blood in 76% and BM in 24%. Results: MAC and SEQ groups had similar ages, ELN scores, numbers of pre-transplant chemotherapy lines and status at transplant. They only differed from the percentage of circulating blasts at transplant (median 1%, range (0-66) in MAC group vs 8%, range (0-93) in SEQ group, p=0.004) and from the time between diagnosis and transplant (median 164 days, range (62-610) and 239 days range (61-3702) respectively, p=0.036). In univariate analysis, type of conditioning regimen (MAC versus SEQ) did not impact post-transplant outcomes: 2-year overall survival (OS) was 37.2% (95% confidence interval (CI): 23.8-50.7%) in MAC patients vs 32.9% (95%CI: 21.4-44.9%) in SEQ patients (p=0.43); 2-year cumulative incidence of relapse was 56.7% (95%CI: 42.2-71.1%) vs 50.1% (95%CI: 37.2-63%) respectively (p=0.89) and 2-year non-relapse mortality was 14.7% (95%CI: 4.5-25%) vs 16.7% (95%CI: 7.1-26.2%) respectively (p=0.46). Grade II-IV acute graft versus host disease (GVHD) occurred more frequently in patients who received MAC: 66.7% vs 36.7% in the SEQ group (p=0.002), there was also a trend for more chronic-GVHD (41.7% vs 25%, p=0.066). Multivariate analysis identified high number of chemotherapy lines (hazard ratio (HR) 1.66, 95%CI 1.11-2, p=0.013) and high percentage of circulating blasts at transplant (HR 1.01, 95%CI 1.003-1, p=0.011), as factors independently associated with poor OS. Heterogeneity analyses performed for OS identified significant interactions between the type of HCT conditioning and BM blast percentage (p=0.01), or CD34+ cell dose (p=0,04), analysed as categorical variables with cut-offs at medians (20% and 6.106/kg, respectively). Though limited by low patients numbers, subgroup analyses suggested that SEQ HCT conferred a higher risk of death in patients with BM blasts > or = to 20% (HR=1.42), but a lower risk (HR=0.59) with BM blasts <20%, compared to MAC. In conclusion, these data confirm that HCT is a valid salvage therapy for relapsed or refractory AML. In patients up to 50 years, both MAC and SEQ conditioning regimens offer similar outcomes, without increased NRM after MAC transplant. Figure 1. Figure 1. Disclosures Mohty: Janssen: Honoraria; Celgene: Honoraria.

scholarly journals Comparison of Allogeneic Stem Cell Transplantation for Transformed Acute Myeloid Leukemia Derived from MDS, CMML or MPN. a Report of the Chronic Malignancies Working Party of EBMT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3499-3499 ◽  
Author(s):  
Nicolaus Kröger ◽  
Diderik-Jan Eikema ◽  
Liesbeth De Wreede ◽  
Anja van Biezen ◽  
Dietrich W. Beelen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Acute Myeloid

Abstract Introduction Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukemia (CMML) can progress to acute myeloid leukemia (transformed AML). The aim of this EBMT registry study was to compare 3 year outcome in patients with transformed AMLwho received allogeneic stem cell transplantation according to the primary disease. Patients and Methods Within the European Society of Blood and Marrow Transplantation (EBMT) registry, we found 4214 patients (female: 39%, male: 61%) with transformed acute myeloid leukemia, who received allogeneic stem cell transplantation between 2000 and 2014. The primary disease was MDS (n=3541), CMML (n=251) or MPN (n=422). The median age at transplantation was 58 years (range, 18-79) and 59% received a reduced intensity (RIC) conditioning regimen. The majority of the patients received stem cells from an unrelated donor (62%) and 50% were in complete remission at time of transplantation. Within the different groups of primary diseases, MDS patients were more often in CR (53%) than patients with CMML (47%) or MPN (43%). RIC was also more frequently used in MDS patients (65%), than in CMML (64%) and MPN patients (58%). Results After a median follow up of 46.5 months , the estimated 3 year relapse-free (RFS) and overall survival (OS) for the entire group was 36% (95%CI: 34-38%) and 40% (95% CI: 33-42%), respectively.The cumulative incidence of relapse and non-relapse mortality (NRM) was 37% (95% CI: 35-39%) and 27% (95% CI: 26-29%), respectively. In a univariate analysis, patients with primary disease MDS had a significant better 3 year OS and RFS (41% and 37%) than patients with CMML (36% and 30) and MPN (32% and 25%) (p<0.001), due to a significant lower incidence of relapse at 3 years (35% vs 43% vs 50%, p<0.001). Other risk factors for worse OS were higher patient's age (>60 years), unrelated donor, not being in complete remission and low Karnofsky index (< 80%), while T-cell depletion, intensity of the conditioning regimen and TBI as conditioning regimen did not influence survival significantly. In a multivariate analysis for OS beside age >60 years (HR 1.31; 95% CI: 1.13-1.52, p<0.001), unrelated donor (HR 1.12; 95% CI: 1.04-1.23, p=0.005), CMV +/- constellation (HR 1.13; 95%CI: 0.99-1.28, p=0.05), Karnofsky index > 80 (HR 0.66; 95% CI: 0.58-0.74, p< 0.001), non CR (HR 1.50; 95% CI: 1.38-1.63, p<0.001) PBSC as stem cell source (HR 0.86; 95% CI:0.75-0.97, p=0.02) and transformed AML from MPN (HR 1.24; 95% CI: 1.085-1.41, p=0.002) remained a significant factor in comparison to transformed AML from MDS, while outcome of transformed AML from CMML did not reach statistical significance in comparison to MDS (HR 1.10; 95% CI: 0.933-1.30, p=0.25) Conclusion This large EBMT registry study demonstrates that the primary underlying disease influence outcome of transformed acute myeloid leukemia in addition to other risk factors. Disclosures Kröger: Novartis: Honoraria, Research Funding. Maertens:Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Amgen: Consultancy. Kobbe:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding.

Allogeneic Stem Cell Transplantation Confers a Favorable Outcome in Patients with NPM1 Positive Acute Myeloid Leukemia: Results From a Donor Vs. No-Donor Analysis of 309 Patients Treated in the SAL AML-2003 Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 493-493
Author(s):  
Christoph Röllig ◽  
Martin Bornhäuser ◽  
Christian Thiede ◽  
Michael Kramer ◽  
Anthony Ho ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Multivariate Analyses ◽  
Normal Karyotype ◽  
Disease Status ◽  
Unrelated Donor ◽  
Intermediate Risk ◽  
No Donor ◽  
Acute Myeloid

Abstract Abstract 493 Background: According to retrospective analyses, the presence of a mutated Nucleophosmin-1 gene (NPM1+) in acute myeloid leukemia (AML) is associated with a favorable prognosis, particularly in the absence of an FLT3-ITD mutation (FLT3-ITD-). Therefore, AML with NPM1+/FLT3-ITD- and normal karyotype has been classified as favorable risk in current prognostic classifications. In order to assess the predictive value with regard to allogeneic stem cell transplantation (allo SCT), we compared the clinical course of 309 NPM1+ AML patients eligible for allo SCT in a donor versus no-donor analysis. Patients and Methods: Patients diagnosed with AML, aged 18–60 years, and treated in the AML 2003 trial of the Study Alliance Leukemia (SAL) were analyzed. According to the risk-adapted treatment strategy of the trial, cytogenetically intermediate-risk (IR) and adverse-risk (AR) patients should receive an allo SCT as consolidation treatment if an HLA-identical-sibling donor (IR) or HLA-matched related or unrelated donor (AR) was available. Patients with no available donor received high-dose cytarabine-based consolidation or autologous SCT. In order to avoid selection bias in an as-treated analysis of transplanted versus non-transplanted patients, we compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor in a donor-no-donor analysis. Survival analyses were performed using the Kaplan-Meier method including log-rank tests for significance testing. Cox regression models and Wald tests were used for multivariate analyses on the influence of potential prognostic variables on the outcomes. Results: Of 1182 patients enrolled in the AML 2003 trial between December 2003 and November 2009, 375 were NPM1+ (32%), and 309 patients were eligible for evaluation for the donor vs. no-donor analysis. Their median age was 49 years, 304 patients had an intermediate-risk karyotype according to MRC criteria (98%), and amongst them there were 277 patients with a normal karyotype (90%). The FLT3-ITD mutation was present in 144 patients (37%). A donor was identified for 77 patients (25%), of whom 57 actually received allo SCT as first consolidation (74%). The no-donor group consisted of 232 patients. Age, disease status, cytogenetic profile, and FLT3-ITD incidence were equally distributed between the two groups. Median follow up was 41 months (3.4 years). The 3-year RFS in the donor and no-donor groups was 72% (95%–CI 61%–82%) and 47% (95%–CI 40%–55%), respectively. (p=0.007). The OS in the donor and no-donor groups were 70% (95%–CI 59%–81%) versus 60% (95%–CI 54%–67%) after 3 years, and 70% (95%–CI 59%–81%) versus 53% (95%–CI 45%–61%) after 5 years (p=0.138). In multivariate analyses, the presence of a donor as a prerequisite for allo SCT retained its statistically significant favorable influence on RFS (HR=0.56) even after adjustment for established risk factors such as FLT3-ITD, cytogenetic risk, WBC, LDH, age, and disease status. In patients with normal karyotype and NPM1+/FLT3-ITD- (n=152), the 3-year RFS in the donor and no-donor groups was 87% (95%–CI 77%–97%) and 53% (95%–CI 42%–63%), respectively (p=0.001). Conclusions: According to our results, allo SCT leads to a significantly prolonged RFS in NPM1+ AML patients with a pronounced effect even in NPM1+/FLT3-ITD- patients. The absence of a statistically significant difference in OS is most likely due to the fact that relapsed NPM1+ patients responded well to salvage treatment, particularly to allo SCT from an unrelated donor. Our data suggest that patients with NPM1+ AML who have a well-matched donor benefit from allo SCT in first remission. This hypothesis is currently being tested prospectively in a randomized controlled trial (“ETAL-1”, NCT01246752) evaluating allo SCT in all intermediate-risk AML patients with a well-matched sibling or unrelated donor identified until the achievement of first CR. Disclosures: No relevant conflicts of interest to declare.

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