Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome: a propensity score-matched analysis

2021 ◽  
Author(s):  
Shuhei Kurosawa ◽  
Yoshimitsu Shimomura ◽  
Hidehiro Itonaga ◽  
Yuho Najima ◽  
Takeshi Kobayashi ◽  
...  
Keyword(s):  
Propensity Score ◽  
Myelodysplastic Syndrome ◽  
Myeloablative Conditioning

scholarly journals IMPACT OF CONDITIONING INTENSITY AND GENOMICS ON RELAPSE AFTER ALLOGENEIC TRANSPLANTATION FOR PATIENTS WITH MYELODYSPLASTIC SYNDROME

2020 ◽  
Author(s):  
Laura W Dillon ◽  
Gege Gui ◽  
Brent R Logan ◽  
Mingwei Fei ◽  
Jack Ghannam ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Hematopoietic Cell Transplantation ◽  
Allogeneic Transplantation ◽  
Marrow Transplant ◽  
Phase Iii ◽  
Myeloablative Conditioning ◽  
Conditioning Intensity ◽  
The Impact ◽  
Relapse Rates ◽  
Reduced Intensity

Myelodysplastic Syndrome (MDS) patients are at risk of relapse after allogeneic hematopoietic cell transplantation (alloHCT). The utility of ultra-deep genomic testing to predict, and the impact of conditioning intensity to prevent, MDS relapse are unknown. Targeted error-corrected DNA sequencing was performed on pre-conditioning blood samples from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901 phase III randomized clinical trial which compared outcomes by alloHCT conditioning intensity in adult patients with less than 5% marrow myeloblasts and no leukemic myeloblasts in blood on morphological analysis at the time of pre-transplant assessment. Using a previously described set of 10 gene regions, 42% of patients had mutations detectable prior to randomization to reduced intensity or myeloablative conditioning. Testing positive was associated with increased rates of relapse and decreased overall survival. In those testing positive, relapse rates were higher and relapse-free survival was lower in reduced intensity versus myeloablative conditioning arms. Testing additional genes, including those associated with MDS, did not improve prognostication. This study provides evidence that post-transplant relapse rates in MDS patients are highest in those with pre-transplant genomic evidence of high-risk disease. In those testing positive, randomization to myeloablative conditioning lowered but did not eliminate relapse risk.

Propensity Score Matching Analysis Comparing Reduced Intensity Versus Myeloablative Conditioning in AML/MDS Patients Transplanted with Fludarabine-Busulfan-Low Dose Total Body Irradiation Based Regimen

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3870-3870
Author(s):  
Hassan Sibai ◽  
Fotios V. Michelis ◽  
Nada Hamad ◽  
Jieun Uhm ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
Propensity Score ◽  
Propensity Score Matching ◽  
Low Dose ◽  
Risk Group ◽  
Case Control ◽  
Period Effect ◽  
Myeloablative Conditioning ◽  
Propensity Score Matching Analysis ◽  
Donor Type ◽  
Total Body

Abstract Background: Allogeneic hematopoietic cell transplantation (HCT) is an effective therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome (AML/MDS). There is controversy over whether reduced intensity conditioning (RIC) results in similar outcomes to myeloablative conditioning (MAC), especially regarding relapse risk. It is difficult to identify the specific cause of the transplant failure rate in RIC patients amongst the multiple possible factors including relapse risk due to disease characteristics of older pts with AML/MDS, or multiple comorbidities in the population receiving RIC, resulting in higher morbidity and mortality, versus expected lower risk of regimen-related toxicity. In order to overcome this, we used a propensity score matching analysis in this study. Methods: A total of 248 patients transplanted for AML or MDS at the Princess Margret Cancer Center between 2009 and 2013 were included in this analysis. Inclusion was restricted to patients receiving Fludarabine/Busulfan plus low dose total body irradiation (TBI) with either RIC conditioning (Fludarabine 30mg/m2/day for 4 days, Busulfan 3.2mg/kg/day for 2 days and TBI 200 cGy n=121) or MAC conditioning (Fludarabine 50mg/m2/day for 4 days, Busulfan 3.2mg/kg/day for 4 days and TBI 400 cGy; n=127). The RIC and MAC groups were compared for overall survival (OS), non-relapse mortality (NRM) and relapse. Propensity score matching (PSM) analysis is used to adjust for the risk factors which affect the choice of treatment between different treatment options. Using PSM analysis, we performed a case-control study with well-balanced pairs of RIC and MAC patients. Pre-transplant variables included in the PSM were age at HCT, HCT-Comorbidity Index (HCT-CI), complete remission status (CR) at HCT, diagnosis (AML vs MDS), cytogenetic risk group (high-risk vs others), donor type (related vs unrelated) and period effect (transplant year). A total of 39 case-control pairs were selected within 0.2 of a difference in propensity score. Paired analysis was adopted throughout the PSM analysis for survival. RESULTS: With a median follow-up of 18 months among survivors in the overall population (n=248), the 2-year OS, NRM and relapse incidence rates were 48.0±3.6%, 34.6±3.6% and 24.8±3.5% respectively There was no difference between the 2 groups in OS (45.2±5.0% in RIC vs 51.7±5.2% in MAC at 2 years; p=0.541) or NRM (32.9±5.2% in RIC vs 35.7±4.9% in MAC at 2 years; p=0.504). However, there was a higher incidence of relapse in the RIC group (31.5±5.1% in RIC vs 18.2±4.8% in MAC at 2 years; p=0.033) Demographic and transplant characteristics were imbalanced between the 2 groups within the overall population, including older age (P=<0.001), higher HCT-CI score (p=0.002) and more related donors in the RIC group (p=0.02). However, no differences were observed in CR status at HCT (p=0.110), subtype of diagnosis (AML vs MDS, p=0.174), or cytogenetic risk group (p=0.278). To overcome baseline imbalances we used a PSM analysis, and 39 case-control pairs (n=78) were selected. All pre-transplant variables became well balanced after propensity score matching, i.e. there were no differences in age (p=0.537), HCT-CI (p=0.931), CR status at HCT (p=0.655), diagnosis (p=0.774), cytogenetic risk group (p=0.784), donor type (p=0.496) or period effect (p=0.984). In the propensity score matched patients, there were no differences in OS (58.0±8.8% in RIC vs 50.9±8.1% in MAC at 2 years; p=0.554), NRM (28.0±8.2% in RIC vs 32.8±7.8% in MAC at 2 years; p=0.688), or relapse (17.8±6.7% in RIC vs 18.0±6.8% in MAC at 2 years; p=0.635). Conclusion: These results suggest, based on a propensity score matching analysis, that the outcomes of a Fludarabine/Busulfan plus low dose TBI based‎ RIC HCT for AML/MDS are equivalent to a Fludarabine/Busulfan plus low dose TBI based MAC with regards to the risk of relapse, NRM, and OS. Disclosures No relevant conflicts of interest to declare.

Induction chemotherapy followed by allogeneic HCT versus upfront allogeneic HCT for advanced myelodysplastic syndrome: A propensity score matched analysis

2018 ◽  
Vol 37 (1) ◽  
pp. 85-95
Author(s):  
Takaaki Konuma ◽  
Yoshimitsu Shimomura ◽  
Yukiyasu Ozawa ◽  
Yasunori Ueda ◽  
Naoyuki Uchida ◽  
...  
Keyword(s):  
Propensity Score ◽  
Myelodysplastic Syndrome ◽  
Induction Chemotherapy ◽  
Allogeneic Hct

Effects of the Order of Administration of Total Body Irradiation and Cyclophosphamide on the Outcome of Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3900-3900
Author(s):  
Kenji Motohashi ◽  
Shin Fujisawa ◽  
Makoto Onizuka ◽  
Shinichi Kako ◽  
Emiko Sakaida ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Chronic Gvhd ◽  
Sinusoidal Obstruction Syndrome ◽  
Myeloablative Conditioning ◽  
Allogeneic Hsct ◽  
High Risk Disease ◽  
Conditioning Regimens ◽  
Total Body ◽  
Order Of Administration

Abstract Background and objectives: Total body irradiation (TBI) combined with cyclophosphamide (CY) is one of the most common myeloablative conditioning regimens used in allogeneic hematopoietic stem-cell transplantation (HSCT) for treating hematological malignancies. However, it remains unclear whether the order of administrating TBI and CY has an effect on the outcome in clinical transplantation. The aim of this study is to clarify the effects of the order of TBI and CY administration on the outcome of allogeneic HSCT. Patients and Methods: We retrospectively investigated the clinical outcome of 504 adult patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and myelodysplastic syndrome who received allogeneic HSCT with myeloablative conditioning regimens consisting of TBI and CY at the transplant centers participating in the Kanto Study Group on Cell Therapy between January 2001 and August 2012. Patients were divided into two groups based on the order in which TBI and CY were administered. The outcome of HSCT and incidences of acute and chronic GVHD, sinusoidal obstruction syndrome / veno-occlusive disease, and idiopathic pneumonia were compared between the two groups.Patients who underwent HSCT during the first or second remission of acute leukemia or refractory anemia of myelodysplastic syndrome were considered as having standard-risk disease. All other conditions were considered as high-risk disease. Results: A total of 218 patients received CY before TBI (CY-TBI) and 286 received CY after TBI (TBI-CY). AML was more common in the CY-TBI group (62.8%) compared with the TBI-CY group (51.0%), and ALL was less common in the CY-TBI group (25.7%) compared with the TBI-CY group (37.8%; P = 0.013). High-risk disease was more frequent in the CY-TBI group (38.5%) compared with the TBI-CY group (23.4%; P < 0.001). The proportion of unrelated bone marrow (54.6% vs. 43.4%) and cord blood transplantation (22.9% vs. 17.8) were higher among patients in the CY-TBI group than in the TBI-CY group (P = 0.0014). TBI was administered at a dose of 12 Gy in 212 patients (97.2%) in the CY-TBI group and 266 patients (93.0%) in the TBI-CY group (P = 0.013). More patients received TBI administered in six fractions in the CY-TBI group (72.9%) than in the TBI-CY group (53.1%; P < 0.001). Female to female transplantation was lower in the CY-TBI (13.3%) group compared with the TBI-CY group (24.1%; P = 0.023). Age, gender, GVHD prophylaxis, and blood mismatch were not significantly different between the two groups. The order in which TBI and CY was administered did not affect the incidence of grades II–IV acute GVHD (45.3% vs. 49.3% at day 100; P = 0.28) and chronic GVHD (36.0% vs. 43.8% at 2 years; P = 0.10), overall survival (52.4% vs. 53.4% at 5 years; P = 0.44), disease-free survival (50.5% vs. 51.5% at 5 years; P = 0.58), relapse rate (30.2% vs. 31.8% at 5 years; P = 0.96) and non-relapse mortality (19.3% vs. 16.7% at 5 years; P = 0.52) in the two groups (CY-TBI and TBI-CY, respectively) by univariate analysis. Moreover, the cumulative incidences of sinusoidal obstruction syndrome / veno-occlusive disease (4.1% vs. 3.8%; P = 0.81) and idiopathic pneumonia were comparable (3.1% vs. 3.4%; P = 0.87) between the two groups (CY-TBI and TBI-CY, respectively). Conclusions: This study demonstrates that the order of administration of TBI and CY does not have an effect on the outcome of allogeneic HSCT. Further studies are warranted to confirm this result. Disclosures No relevant conflicts of interest to declare.

scholarly journals Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study

2018 ◽  
Vol 2 (16) ◽  
pp. 2127-2135 ◽  
Author(s):  
Salyka Sengsayadeth ◽  
Katie S. Gatwood ◽  
Ariane Boumendil ◽  
Myriam Labopin ◽  
Jürgen Finke ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Myeloproliferative Disorders ◽  
Myeloablative Conditioning ◽  
Term Survival ◽  
Long Term Survival ◽  
Secondary Aml ◽  
Key Points ◽  
Conditioning Regimens ◽  
Conditioning Intensity

Key Points Allogeneic HCT can result in long-term survival for patients with sAML and prior MDS/MPN. Myeloablative conditioning regimens should be selected for sAML and patients with prior MDS/MPN whenever possible.

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