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Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch.
Biol Blood Marrow Transplant. 2013 Aug; 19(8):1167-74.BB

Abstract

Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient- and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health-defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI.

Authors+Show Affiliations

Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA. slack.james@mayo.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23664940

Citation

Slack, James L., et al. "Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplantation in Adults Using Fludarabine, Carmustine, Melphalan, and Antithymocyte Globulin: Outcomes Depend On Disease Risk Index but Not Age, Comorbidity Score, Donor Type, or Human Leukocyte Antigen Mismatch." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 19, no. 8, 2013, pp. 1167-74.
Slack JL, Dueck AC, Fauble VD, et al. Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch. Biol Blood Marrow Transplant. 2013;19(8):1167-74.
Slack, J. L., Dueck, A. C., Fauble, V. D., Sproat, L. O., Reeder, C. B., Noel, P., Khera, N., Betcher, J. A., Klein, J. L., Leis, J. F., & Adams, R. H. (2013). Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 19(8), 1167-74. https://doi.org/10.1016/j.bbmt.2013.05.001
Slack JL, et al. Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplantation in Adults Using Fludarabine, Carmustine, Melphalan, and Antithymocyte Globulin: Outcomes Depend On Disease Risk Index but Not Age, Comorbidity Score, Donor Type, or Human Leukocyte Antigen Mismatch. Biol Blood Marrow Transplant. 2013;19(8):1167-74. PubMed PMID: 23664940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch. AU - Slack,James L, AU - Dueck,Amylou C, AU - Fauble,Veena D, AU - Sproat,Lisa O, AU - Reeder,Craig B, AU - Noel,Pierre, AU - Khera,Nandita, AU - Betcher,Jeffery A, AU - Klein,Jared L, AU - Leis,Jose F, AU - Adams,Roberta H, Y1 - 2013/05/07/ PY - 2013/03/03/received PY - 2013/05/01/accepted PY - 2013/5/14/entrez PY - 2013/5/15/pubmed PY - 2014/5/10/medline KW - Allogeneic stem cell transplant KW - Antithymocyte globulin KW - Reduced toxicity conditioning SP - 1167 EP - 74 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 19 IS - 8 N2 - Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient- and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health-defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/23664940/Reduced_toxicity_conditioning_and_allogeneic_stem_cell_transplantation_in_adults_using_fludarabine_carmustine_melphalan_and_antithymocyte_globulin:_outcomes_depend_on_disease_risk_index_but_not_age_comorbidity_score_donor_type_or_human_leukocyte_antigen_mismatch_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(13)00196-1 DB - PRIME DP - Unbound Medicine ER -