HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide

Leo Luznik; Paul V. O'Donnell; Heather J. Symons; Allen R. Chen; M. Susan Leffell; Marianna Zahurak; Ted A. Gooley; Steve Piantadosi; Michele Kaup; Richard F. Ambinder; Carol Ann Huff; William Matsui; Javier Bolaños-Meade; Ivan Borrello; Jonathan D. Powell; Elizabeth Harrington; Sandy Warnock; Mary Flowers; Robert A. Brodsky; Brenda M. Sandmaier; Rainer F. Storb; Richard J. Jones; Ephraim J. Fuchs

doi:10.1016/j.bbmt.2008.03.005

HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide

Leo Luznik, Paul V. O'Donnell, Heather J. Symons, Allen R. Chen, M. Susan Leffell, Marianna Zahurak, Ted A. Gooley, Steve Piantadosi, Michele Kaup, Richard F. Ambinder, Carol Ann Huff, William Matsui, Javier Bolaños-Meade, Ivan Borrello, Jonathan D. Powell, Elizabeth Harrington, Sandy Warnock, Mary Flowers, Robert A. Brodsky, Brenda M. SandmaierRainer F. Storb, Richard J. Jones, Ephraim J. Fuchs

School of Medicine

Research output: Contribution to journal › Article › peer-review

986 Scopus citations

Abstract

We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/μL) and platelet recovery (>20,000/μL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.

Original language	English (US)
Pages (from-to)	641-650
Number of pages	10
Journal	Biology of Blood and Marrow Transplantation
Volume	14
Issue number	6
DOIs	https://doi.org/10.1016/j.bbmt.2008.03.005
State	Published - Jun 2008

Keywords

Bone marrow transplantation
Conditioning regimens
Cyclophosphamide
Histocompatibility antigens
Leukemia
Lymphoma

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2008.03.005

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Luznik, L., O'Donnell, P. V., Symons, H. J., Chen, A. R., Leffell, M. S., Zahurak, M., Gooley, T. A., Piantadosi, S., Kaup, M., Ambinder, R. F., Huff, C. A., Matsui, W., Bolaños-Meade, J., Borrello, I., Powell, J. D., Harrington, E., Warnock, S., Flowers, M., Brodsky, R. A., ... Fuchs, E. J. (2008). HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide. Biology of Blood and Marrow Transplantation, 14(6), 641-650. https://doi.org/10.1016/j.bbmt.2008.03.005

HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide. / Luznik, Leo; O'Donnell, Paul V.; Symons, Heather J. et al.
In: Biology of Blood and Marrow Transplantation, Vol. 14, No. 6, 06.2008, p. 641-650.

Research output: Contribution to journal › Article › peer-review

Luznik, L, O'Donnell, PV, Symons, HJ , Chen, AR , Leffell, MS, Zahurak, M, Gooley, TA, Piantadosi, S, Kaup, M, Ambinder, RF , Huff, CA, Matsui, W, Bolaños-Meade, J, Borrello, I, Powell, JD, Harrington, E, Warnock, S, Flowers, M, Brodsky, RA, Sandmaier, BM, Storb, RF, Jones, RJ & Fuchs, EJ 2008, 'HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide', Biology of Blood and Marrow Transplantation, vol. 14, no. 6, pp. 641-650. https://doi.org/10.1016/j.bbmt.2008.03.005

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title = "HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide",

abstract = "We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/μL) and platelet recovery (>20,000/μL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.",

keywords = "Bone marrow transplantation, Conditioning regimens, Cyclophosphamide, Histocompatibility antigens, Leukemia, Lymphoma",

author = "Leo Luznik and O'Donnell, {Paul V.} and Symons, {Heather J.} and Chen, {Allen R.} and Leffell, {M. Susan} and Marianna Zahurak and Gooley, {Ted A.} and Steve Piantadosi and Michele Kaup and Ambinder, {Richard F.} and Huff, {Carol Ann} and William Matsui and Javier Bola{\~n}os-Meade and Ivan Borrello and Powell, {Jonathan D.} and Elizabeth Harrington and Sandy Warnock and Mary Flowers and Brodsky, {Robert A.} and Sandmaier, {Brenda M.} and Storb, {Rainer F.} and Jones, {Richard J.} and Fuchs, {Ephraim J.}",

note = "Funding Information: This research was supported by grants CA15396, CA18029, HL36444, CA78902, and CA15704 from the NIH, and from Astellas Pharma, Inc. E.J.F. is a Clinical Research Scholar of the Leukemia-Lymphoma Society of America.",

year = "2008",

month = jun,

doi = "10.1016/j.bbmt.2008.03.005",

language = "English (US)",

volume = "14",

pages = "641--650",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

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T1 - HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide

AU - Luznik, Leo

AU - O'Donnell, Paul V.

AU - Symons, Heather J.

AU - Chen, Allen R.

AU - Leffell, M. Susan

AU - Zahurak, Marianna

AU - Gooley, Ted A.

AU - Piantadosi, Steve

AU - Kaup, Michele

AU - Ambinder, Richard F.

AU - Huff, Carol Ann

AU - Matsui, William

AU - Bolaños-Meade, Javier

AU - Borrello, Ivan

AU - Powell, Jonathan D.

AU - Harrington, Elizabeth

AU - Warnock, Sandy

AU - Flowers, Mary

AU - Brodsky, Robert A.

AU - Sandmaier, Brenda M.

AU - Storb, Rainer F.

AU - Jones, Richard J.

AU - Fuchs, Ephraim J.

N1 - Funding Information: This research was supported by grants CA15396, CA18029, HL36444, CA78902, and CA15704 from the NIH, and from Astellas Pharma, Inc. E.J.F. is a Clinical Research Scholar of the Leukemia-Lymphoma Society of America.

PY - 2008/6

Y1 - 2008/6

N2 - We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/μL) and platelet recovery (>20,000/μL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.

AB - We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/μL) and platelet recovery (>20,000/μL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.

KW - Bone marrow transplantation

KW - Conditioning regimens

KW - Cyclophosphamide

KW - Histocompatibility antigens

KW - Leukemia

KW - Lymphoma

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HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide

Abstract

Keywords

ASJC Scopus subject areas

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