Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation (RISCT) using antilymphocyte antibodies in patients with high-risk acute myeloid leukemia (AML)

Popat, Uday; Heslop, Helen E.; Durett, April; May, R.; Krance, Robert A.; Brenner, Malcolm K.; Carrum, George

doi:10.1038/sj.bmt.1705229

Cited by 16 publications

(8 citation statements)

References 26 publications

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“…Nevertheless, its effect can be hampered by drug-associated toxicities, infections or GVHD, particularly in adult patients. FluBU regimen in allo-HSCT for high-risk patients S Chunduri et al Different reduced-intensity conditioning regimens have been developed combining fludarabine with either lowdose TBI or chemotherapy [24][25][26] and have been also utilized in patients at high risk of relapse with the purpose of decreasing the TRM. The use of i.v.…”

Section: Discussionmentioning

confidence: 99%

Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both?

Chunduri

Dobogai

Peace

et al. 2008

Bone Marrow Transplant

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In this study, we utilized a conditioning regimen with fludarabine and myeloablative dose i.v. BU (12.8 mg/kg) (FluBU) in 36 adult patients (median age: 44 years, range: 18-61) with myeloid or lymphoid malignancies at standard risk (n ¼ 10) or high risk of relapse (n ¼ 26), who received an allogeneic hematopoietic SCT (HSCT) from HLA-matched related (n ¼ 16) or unrelated (n ¼ 20) donors. The source of hematopoietic stem cells was peripheral blood in 28 and marrow in 8 cases. Rabbitantithymocyte globulin at 7 mg/kg was utilized in 21 patients. Acute GVHD grade II-IV was observed in 19% of the patients (grade III-IV in 14% of patients) and chronic GVHD in 11 of 30 evaluable patients (37%). At median follow-up of 737 days (range: 152-1737) for alive patients, overall survival rates in standard-and high-risk patients were 80 and 35%, respectively, and event-free survival rates were 70 and 31%, respectively. TRM was 10% in standard-risk and 19% in high-risk patients. Post transplant relapse was observed in 20% standard-risk and in 46% high-risk patients. FluBU conditioning regimen is associated with a limited hematologic and extrahematologic toxicity and with an antitumor activity comparable to other standard myeloablative regimens.

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Section: Discussionmentioning

confidence: 99%

Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both?

Chunduri

Dobogai

Peace

et al. 2008

Bone Marrow Transplant

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“…RIC has been shown to be an effective strategy permitting older and less fit patients access to potentially curative allogeneic HSCT. [7][8][9][10][11] Single-center data indicate that UCB immune cells are sufficient for securing consistent engraftment after RIC. [12][13][14][15][16][17][18] However, data on the relative efficacy of UCB after RIC compared with other donor HSC sources are limited.…”

Section: Introductionmentioning

confidence: 99%

Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes

Brunstein

Eapen

Ahn

et al. 2012

Blood

120

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AbstractWe report the relative efficacy of co-infusing 2 umbilical cord blood units (dUCB) compared with peripheral blood progenitor cells (PBPCs) from 8 of 8 or 7 of 8 HLA-matched unrelated donors. All patients received reduced-intensity conditioning (RIC) regimens. Four treatment groups were evaluated: 4-6 of 6 matched dUCB-TCF (n = 120; TCF = total body irradiation [TBI] 200 cGy + cyclophos-phamide + fludarabine), 4-6 of 6 matched dUCB-other (n = 40; alkylating agent + fludarabine ± TBI), and 8 of 8 (n = 313) and 7 of 8 HLA-matched PBPCs (n = 111). Compared with matched 8 of 8 PBPC transplantations, transplantation-related mortality (TRM), and overall mortality were similar after dUCB-TCF (relative risk [RR] 0.72, P = .72; RR 0.93, P = .60) but higher after dUCB-other RIC (hazard ratio [HR] 2.70, P = .0001; 1.79 P = .004). Compared with 7 of 8 PBPC transplantations, TRM (but not overall mortality) was lower after dUCB-TCF (RR 0.57, P = .04; RR 0.87 P = .41). The probabilities of survival after dUCB-TCF, dUCB-other RIC, and 8 of 8 PBPC and 7 of 8 PBPC transplantations were 38%, 19%, 44%, and 37%, respectively. With similar survival after 8 of 8, 7 of 8 matched PBPCs, and dUCB-TCF, these data support use of dUCB-TCF transplantation in adults with acute leukemia who may benefit from RIC transplantation urgently or lack a 7-8 of 8 unrelated donor.

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“…[1][2][3][4][5] For patients lacking an HLAmatched sibling, it is routine to initiate an unrelated donor search. However, a suitably matched unrelated donor cannot be identified for as many as one-third of patients, even more for members of ethnic minorities.…”

Section: Introductionmentioning

confidence: 99%

Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts

Brunstein

Fuchs

Carter

et al. 2011

Blood

548

402

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with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n ‫؍‬ 50) and 62% and 48%, respectively, after Haplomarrow transplantation (n ‫؍‬ 50). The day ؉56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplomarrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies.

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Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation (RISCT) using antilymphocyte antibodies in patients with high-risk acute myeloid leukemia (AML)

Cited by 16 publications

References 26 publications

Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both?

Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both?

Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes

Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts

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