Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy

Biggs, J. C.; Horowitz, M.; Rp, Gale; Ash, RC; Atkinson, K; Helbig, W; Jacobsen, N; Gl, Phillips; Rimm, AA; Ringdén, Olle

doi:10.1182/blood.v80.4.1090.1090

Cited by 147 publications

(51 citation statements)

References 5 publications

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“…The association of advanced leukaemia and the occurrence of severe GVHD has also been reported by Nash et al (1992). Cumulative effects of prior chemotherapy and reduced tolerance of the intensive conditioning regimens used at BMT (Biggs et al, 1992;Bortin et al, 1981;Clift et al, 1987Clift et al, , 1990Clift et al, , 1991Deeg et al, 1991;Nash et al, 1992) may account in part for the severe GVHD seen in patients transplanted for advanced leukaemia.…”

Section: Discussionmentioning

confidence: 89%

Bone marrow transplantation for chronic myeloid leukaemia: the effects of differing criteria for defining chronic phase on probabilities of survival and relapse

et al. 1997

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Summary.We studied actuarial survival and relapse in 251 patients with chronic myeloid leukaemia (CML) treated by bone marrow transplantation (BMT) from HLA-identical sibling donors at a single institution. According to the institutional criteria used to define disease phase at the time of BMT, the 5-year probabilities of survival were 58 . 1% (95% confidence interval 50-66%) for 205 chronic-phase patients and 21 . 5% (95%CI 12-37%) for 46 advanced-phase patients (P < 0 . 00001); the corresponding values for relapse were 34 . 8% (95%CI 27-44%) versus 72 . 7% (95%CI 46-89%). When disease phase was defined strictly according to the criteria of the International Bone Marrow Transplant Registry, the survival for 154 chronic-phase patients increased to 60 . 1% (95%CI 51-69%) and that for 97 advanced-phase patients increased to 37 . 6% (95%CI 28-48%). There was a parallel change in probabilities of relapse in the two patient groups (33 . 9% [95%CI 25-44%] and 51 . 3% [95%CI 37-66%], respectively). We also observed that patients transplanted in advanced phase had a higher incidence of grades III-IV acute graft-versus-host disease (P ¼ 0 . 001) and transplant-related mortality (P ¼ 0 . 02) than those undergoing BMT for chronic-phase disease. We recommend that transplant centres reporting results of BMT should always specify the precise criteria used for defining disease phase in order to ensure that results between different centres are strictly comparable.

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Section: Discussionmentioning

confidence: 89%

Bone marrow transplantation for chronic myeloid leukaemia: the effects of differing criteria for defining chronic phase on probabilities of survival and relapse

et al. 1997

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“…Thus, our sequential approach M. Mohty et al 188 haematologica | 2017; 102(1) 35 The 2-year overall survival rate was 38%, similar to the 42% reported by Schmid et al using the FLAMSA sequential regimen, 12 and superior to the 20-30% reported after standard MAC allogeneic SCT. 8,10,29 Similarly, Middeke et. al.…”

Section: Discussionmentioning

confidence: 93%

Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

et al. 2016

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T he prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m 2 /day) and cytosine arabinoside (1 g/m 2 /day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33-71) at 1 year and 38% (95% CI: 18-46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26-64) at 1 year and 29% (95% CI: 13-48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1-24) at 1 year and 12% (95% CI: 3-19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. IntroductionThe prognosis of patients with acute myeloid leukemia (AML) in primary treatment failure remains very poor. Primary treatment failure or primary refractory AML is defined by failure to achieve a complete hematologic remission (CR) after one or two courses of induction chemotherapy.1,2 For these patients, the chance of achieving a CR with another standard or conventional treatment, including the use of intermediate-or high-dose cytosine arabinoside (Ara-C) alone or in combination with an ABSTRACT © Ferrata Storti Foundationanthracycline, fludarabine or gemtuzumab-ozogamicin, is 10-20% at best. The overall survival rate at 1 year is less than 20%, with a median survival of less than 6 months.3-5

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“…Few retrospective studies or case series limited to a small subset of highly selected patients receiving a myeloablative allo-HCT have been reported in the literature. [43][44][45] A large CIBMTR study has recently reported a remarkable 3-year OS rate of 42% with matched-sibling myeloablative allo-HCT in a subset of refractory AML patients who had a good performance status, no circulating blasts, a prior CR duration of > 6 months, and no poor-risk cytogenetics. 46 The role of RIC in refractory AML, however, is more controversial.…”

Section: The Role Of Ric Transplantation In Refractory Amlmentioning

confidence: 99%

Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Myeloid Leukemia

2011

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Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy

Cited by 147 publications

References 5 publications

Bone marrow transplantation for chronic myeloid leukaemia: the effects of differing criteria for defining chronic phase on probabilities of survival and relapse

Bone marrow transplantation for chronic myeloid leukaemia: the effects of differing criteria for defining chronic phase on probabilities of survival and relapse

Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Myeloid Leukemia

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