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1.
Allogeneic Hematopoietic Stem-Cell Transplantation Improves Disease-Free Survival Compared to Pediatric-Inspired Berlin-Frankfurt-Münster Chemotherapy in Adult Acute Lymphoblastic Leukemia
Aladag, E., Aktimur, S. H., Aydin, Ö, Demiroglu, H., Buyukasik, Y., Aksu, S., Ozcebe, O. I., Haznedaroglu, I. C., Sayinalp, N., Turgut, M., et al
Clinical lymphoma, myeloma & leukemia. 2021
Abstract
INTRODUCTION Acute 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 METHODS Forty-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. RESULTS There 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 × 10(9)/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). CONCLUSION AHSCT 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.
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2.
Long-term Outcomes of Allogeneic Hematopoietic Cell transplantation with Fludarabine and Melphalan Conditioning and Tacrolimus/Sirolimus as GVHD prophylaxis in Patients with Acute Lymphoblastic Leukemia
Mei, M., Tsai, N. C., Mokhtari, S., Malki, M. M. A., Ali, H., Salhotra, A., Sandhu, K., Khaled, S., Smith, E., Snyder, D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Acute lymphoblastic leukemia (ALL) is associated with poor survival in older adults, and allogeneic hematopoietic cell transplant (HCT) with reduced intensity conditioning (RIC) has been an increasingly utilized strategy in this population. At City of Hope, we conducted a retrospective analysis of 72 patients who underwent allogeneic HCT with fludarabine and melphalan (FluMel) as conditioning regimen between 2005 and 2018, from either a matched sibling or fully matched unrelated donor while in complete remission. Tacrolimus and sirolimus (T/S) was used as graft-versus-host disease (GVHD) prophylaxis. Overall survival and progression-free survival at 4 years post-HCT were 58% and 44%, respectively. The cumulative incidences of relapse/progression (CIR) and non-relapse mortality at 4 years were 34% and 22%, respectively. Patients with Philadelphia chromosome-positive (Ph+) ALL had a significantly lower CIR (20% vs. 48% for patients with Philadelphia chromosome-negative (Ph-) status, p=0.007). In conclusion, RIC HCT with FluMel conditioning and T/S GVHD prophylaxis was associated with favorable outcomes in patients with Ph+ ALL and should be considered as a viable consolidative therapy for adult patients with ALL.
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3.
Comparison of reduced-intensity conditioning regimens in patients with acute lymphoblastic leukemia >45 years undergoing allogeneic stem cell transplantation-a retrospective study by the Acute Leukemia Working Party of EBMT
Peric, Z., Labopin, M., Peczynski, C., Polge, E., Cornelissen, J., Carpenter, B., Potter, M., Malladi, R., Byrne, J., Schouten, H., et al
Bone marrow transplantation. 2020
Abstract
The optimal reduced-intensity conditioning (RIC) for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively analyzed 417 patients > 45 years with ALL in first complete remission who underwent a matched sibling or unrelated allo-HSCT and compared outcomes between fludarabine/busulfan (FLUBU, n = 127), fludarabine/melphalan (FLUMEL, n = 190), and fludarabine-TBI (FLUTBI, n = 100) conditioning. At 2 years, there were no differences between the groups in terms of cumulative incidence (CI) of relapse (40% for FLUBU vs 36% for FLUMEL vs 41% for FLUTBI, p = 0.21); transplant-related mortality (TRM) (18% for FLUBU, 22% for FLUMEL, 14% for FLUTBI, p = 0.09); overall survival (55% for FLUBU, 50% for FLUMEL, 60% for FLUTBI, p = 0.62) or leukemia-free survival (43% for FLUBU, 42% for FLUMEL, 45% for FLUTBI, p = 0.99), but GVHD-relapse-free survival was significantly lower in the FLUTBI group than FLUBU and FLUMEL group (18% vs 35% vs 28%, p = 0.02). However, this difference was lost in the multivariate analysis when adjusted for the in vivo T-cell depletion. Finally, the FLUMEL regimen was shown to be an independent risk factor for a higher TRM (HR 1.97, 95% CI 1.05-3.72, p = 0.04). We conclude that the three most popular RIC regimens yield similar transplant outcomes.
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4.
A new pre-emptive TKIs strategy for preventing relapse based on BCR/ABL monitoring for Ph+ALL undergoing allo-HCT: a prospective clinical cohort study
Liu, H., Xuan, L., Lin, R., Deng, L., Fan, Z., Nie, D., Li, X., Liang, X., Xu, D., Zhang, Y., et al
Leukemia. 2020
Abstract
Relapse is a major cause of treatment failure in Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to evaluate the effect of a new pre-emptive tyrosine kinase inhibitors (TKIs) strategy on relapse in Ph+ALL patients with complete remission undergoing allo-HCT. Pre-emptive TKIs initiation was based on BCR/ABL molecular monitoring. TKIs choice was based on BCR/ABL mutations. Donor lymphocyte infusion was recommended in those with poor response to TKIs. Prophylactic TKIs from historical data were as control. The primary endpoint was relapse. One hundred and sixty-seven Ph+ALL patients were enrolled in this study, including 103 in the pre-emptive group and 64 in the prophylactic group. The 3-year cumulative incidence of relapse was 11% and 31% in the pre-emptive and prophylactic groups (P?=?0.001), respectively. The 3-year overall survival (OS) was 87% and 66% (P?=?0.001), and leukemia-free survival (LFS) was 83% and 61% (P?=?0.000), respectively, in the pre-emptive and prophylactic groups. Multivariate analysis showed that the pre-emptive strategy was the protective factor for relapse, OS, and LFS (P?=?0.005, P?=?0.005, and P?=?0.003, respectively). Our data suggest that this new pre-emptive TKIs strategy based on BCR/ABL molecular monitoring might reduce relapse and improve survival for Ph+ALL patients undergoing allo-HCT. ClinicalTrials.Gov Identifier (NCT01883219).
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5.
Reduced-Intensity Conditioning with Busulfan and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Leukemia
Lee, S. S., Jung, S. H., Do, Y. R., Kim, D. S., Lee, J. H., Park, H. S., Moon, J. H., Yi, J. H., Park, Y., Koh, Y., et al
Yonsei medical journal. 2020;61(6):452-459
Abstract
PURPOSE Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation. MATERIALS AND METHODS Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m(2)/day of fludarabine for 5 or 6 days were analyzed. RESULTS The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26-1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II-IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively. CONCLUSION RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.
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6.
Once-a-day fractionated total-body irradiation: A regimen tailored to local logistics in allogeneic stem cell transplantation for acute lymphoblastic leukemia
Ben Abdeljelil, N., Ladeb, S., Dahmani, T., Kochbati, L., Lakhal, A., El Fatmi, R., Torjemane, L., Belloumi, D., Besbes, M., El Benna, F., et al
Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology. 2020;25(3):436-441
Abstract
Aim: The objective of the study was to estimate the cumulative incidence (CI) of relapse, relapse-free survival (RFS) and overall survival (OS) in ALL patients after a once-a-day fractionated TBI (F-TBI) regimen with 9.9Gy. The secondary objectives were evaluation of short and long-term toxicity and non-relapse mortality (NRM). Background: Total body irradiation (TBI), as a part of the conditioning regimen before allogeneic stem cell transplantation (ASCT) for acute lymphoblastic leukemia (ALL), allows disease control by eradicating residual blast cells in the transplant recipient. Materials and methods: Retrospective study conducted in patients with ALL who received between March 2003 and December 2013 a conditioning regimen with F-TBI and chemotherapy. Irradiation was delivered with 3.3Gy once-a-day for three consecutive days. Results: Eighty-seven patients were included. The median age was 19 years (range: 5-49 years). The 3-year CI of relapse was 30%. The estimated 3-year RFS and OS were 54% and 58%, respectively. Cumulative incidence of acute graft-versus-host disease (aGVHD) grade II-IV and chronic GVHD (cGVHD) was 31% and 40%, respectively. Interstitial pneumonitis was observed in 2 patients. The 3-year CI of NRM was 16%. In multivariate analysis, cGVHD was associated with a lower CI of relapse (RR=0.26, 95% CI: 0.07-0.95, p=0.04). High-risk cytogenetics was associated with a lower RFS (RR=2, 95 CI: 1.04-3.84, p=0.03). Grade II-IV aGVHD was an independent predictor of higher CI of NRM (RR=6.7, 95% CI: 1.4-31.7, p=0.02). Conclusions: Once-a-day F-TBI regimen is effective, safe and practical in patients who underwent ASCT for ALL.
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7.
Reduced-intensity conditioning is a reasonable alternative for Philadelphia chromosome-positive acute lymphoblastic leukemia among elderly patients who have achieved negative minimal residual disease: a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSHCT
Akahoshi, Y., Nishiwaki, S., Arai, Y., Harada, K., Najima, Y., Kanda, Y., Shono, K., Ota, S., Fukuda, T., Uchida, N., et al
Bone marrow transplantation. 2020
Abstract
Reduced-intensity conditioning (RIC) regimens have been widely used for allogeneic hematopoietic cell transplantation (HCT) in elderly patients. After the emergence of tyrosine kinase inhibitor (TKI), most patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) now achieve negative results for minimal residual disease (MRD) at HCT. In this study, we evaluated patients aged 50 years or more with Ph-positive ALL who received TKI before HCT, achieved negative-MRD at HCT, and underwent their first allogeneic HCT between 2008 and 2017. In total, 90 and 136 patients who received myeloablative conditioning (MAC) and a RIC regimen, respectively, were included. The median age of patients with MAC and RIC was 54 and 60 years, respectively. Even in multivariate analyses, RIC was not significantly associated with overall mortality (hazard ratio [HR], 1.09; P = 0.724), hematological relapse (HR, 1.97; P = 0.170), or non-relapse mortality (HR, 0.84; P = 0.540). Subgroup analyses suggested that RIC resulted in superior overall survival due to a lower incidence of non-relapse mortality in patients with a poor performance status or a high HCT comorbidity index. In conclusion, RIC is a reasonable option for elderly patients with negative-MRD at HCT.
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8.
Irradiation free conditioning regimen is associated with high relapse rate in Egyptian patients with acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation
Abdelaty, M. M., Gawaly, A., Fathy, G. M., Kabbash, I., Taha, A.
Journal of the Egyptian National Cancer Institute. 2020;32(1):28
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment for adult patients with acute lymphoblastic leukemia (ALL). Cyclophosphamide plus total body irradiation (TBI/Cy) or plus busulfan (Bu/Cy) is a widely used pre-transplant conditioning regimen for ALL. We retrospectively compared the overall survival (OS), disease-free survival (DFS), and other transplant outcomes of allo-HSCT in 119 adult patients with ALL who received an HLA-matched sibling allo-HSCT using TBI-based versus non-TBI-based conditioning regimens. Patients were divided into two groups by their conditioning regimen: TBI/Cy or Bu/Cy. RESULTS Median OS was 11 months in the TBI/Cy group and 6.2 months in the Bu/Cy group. Median DFS was 11.1 months in the TBI group versus 6.8 months in the Bu group, without a statistically significant difference. A higher risk of relapse was observed with the Bu/Cy regimen (HR 2.709, CI 95% 1.106 to 6.638, p = 0.029). Patients who received a transplant in ≥ CR2 were associated with poor DFS. CONCLUSION Despite the high relapse rate in the non-TBI regimen (Bu/Cy), both regimens had no statistically significant differences in OS, DFS, and NRM. Additional prospective studies are indeed warranted to evaluate the long-term outcomes of radiation-free regimens, including oral and intravenous busulfan, and compare these regimens with TBI-based ones.
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9.
Comparing the outcomes between TMLI and non-TMLI conditioning regimens for adult high-risk acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: a single-center experience
Zhao, X., Lu, X., Tang, L., Yan, H., Chen, W., Shi, W., Zhong, Z., You, Y., Xia, L., Hu, Y., et al
Leukemia & lymphoma. 2020;:1-9
Abstract
This study aimed to retrospectively evaluate the outcomes of adult patients with high-risk acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either total marrow and lymphoid irradiation (TMLI)-containing or non-TMLI conditioning regimen. Seventy adult patients with high-risk ALL who received allo-HSCT were enrolled in this study and divided into two groups based on the conditioning regimen type (TMLI group: n = 29 and non-TMLI group: n = 41). We noted significant statistical differences in the 1-year estimated cumulative incidence of relapse (25% vs. 46.5%, p = 0.018), the 1-year estimated overall survival (73.1% vs. 52.6%, p = 0.033) and disease-free survival (65.2% vs. 48.2%, p = 0.026) but found no considerable difference in transplant-related mortality (12% vs. 13.4%, p = 0.619) between patients in the TMLI and non-TMLI groups. The TMLI-containing regimen is safe and alternative for patients with high-risk ALL undergoing allo-HSCT.
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10.
Comparison of reduced-intensity/toxicity conditioning regimens for umbilical cord blood transplantation for lymphoid malignancies
Imahashi, N., Terakura, S., Kondo, E., Kako, S., Uchida, N., Kobayashi, H., Inamoto, Y., Sakai, H., Tanaka, M., Ishikawa, J., et al
Bone marrow transplantation. 2020
Abstract
To investigate which reduced-intensity conditioning (RIC)/reduced-toxicity conditioning (RTC) is superior for umbilical cord blood transplantation (UCBT) for lymphoid malignancies, we retrospectively compared three widely used RIC/RTC regimens: fludarabine/melphalan/total body irradiation (FM-TBI, n = 524), fludarabine/cyclophosphamide/total body irradiation (FC-TBI, n = 96), and fludarabine/busulfan/total body irradiation or melphalan (FB-based, n = 159). Among patients with acute lymphoblastic leukemia (ALL) (n = 314), there were no differences in overall survival (OS) by conditioning regimen. Among patients with malignant lymphoma (ML) (n = 465), FM-TBI and FC-TBI regimens had similar OS, whereas FB-based regimen had lower OS (hazard ratio [HR], 1.73; P < 0.01) than did FM-TBI regimen due to higher non-relapse mortality (HR, 1.72; P = 0.02). In addition, mycophenolate mofetil-containing GVHD prophylaxis was associated with better OS than methotrexate-containing GVHD prophylaxis among patients who received FM-TBI (HR, 0.65; P = 0.03) and FC-TBI (HR, 0.25; P < 0.01) regimens due to a decreased relapse risk. In summary, our results suggest that all three RIC/RTC regimens have comparable clinical outcomes in ALL, while the FM-TBI or FC-TBI regimens combined with mycophenolate mofetil-containing GVHD prophylaxis is preferable in RIC/RTC-UCBT for ML. Large prospective studies are warranted to confirm these results.
