Activity of single-agent melphalan 220-300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma

Gordon L. Phillips; B. R. Meisenberg; D. E. Reece; V. R. Adams; A. Z. Badros; J. L. Brunner; R. G. Fenton; J. Filicko; D. L. Grosso; G. A. Hale; D. S. Howard; V. P. Johnson; A. Kniska; K. W. Marshall; B. Mookerjee; R. Nath; A. P. Rapoport; C. Sarkodee-Adoo; N. Takebe; D. H. Vesole; J. L. Wagner; N. Flomenberg

doi:10.1038/sj.bmt.1704424

Activity of single-agent melphalan 220-300 mg/m² with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma

Gordon L. Phillips, B. R. Meisenberg, D. E. Reece, V. R. Adams, A. Z. Badros, J. L. Brunner, R. G. Fenton, J. Filicko, D. L. Grosso, G. A. Hale, D. S. Howard, V. P. Johnson, A. Kniska, K. W. Marshall, B. Mookerjee, R. Nath, A. P. Rapoport, C. Sarkodee-Adoo, N. Takebe, D. H. VesoleJ. L. Wagner, N. Flomenberg

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

17 Scopus citations

Abstract

High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m² plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D + 100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL + AF + AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D + 1163 (range D + 824 to D + 1630); one of these patients had a nonmyeloablative allograft as consolidation on D + 106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL + AF + AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.

Original language	English
Pages (from-to)	781-787
Number of pages	7
Journal	Bone Marrow Transplantation
Volume	33
Issue number	8
DOIs	https://doi.org/10.1038/sj.bmt.1704424
State	Published - Apr 2004

Bibliographical note

Funding Information:
We thank our patients for their willingness to undergo clinical research studies; our nursing colleagues for their excellent patient care; our medical consultants for their valuable assistance; our data coordinators, and Ms M Coddington, Ms Lynn Stull and Ms Linda Wilkinson for their expert help with manuscript preparation. Finally, we thank Dr J Friedberg for his helpful suggestions with the manuscript. Grant support for this study was provided by the NIH, RO3CA80666 and ALZA.

Keywords

Chemotherapy
Lymphoma
Stem cell transplantation cytoprotection

ASJC Scopus subject areas

Hematology
Transplantation

Access to Document

10.1038/sj.bmt.1704424

Cite this

Phillips, G. L., Meisenberg, B. R., Reece, D. E., Adams, V. R., Badros, A. Z., Brunner, J. L., Fenton, R. G., Filicko, J., Grosso, D. L., Hale, G. A., Howard, D. S., Johnson, V. P., Kniska, A., Marshall, K. W., Mookerjee, B., Nath, R., Rapoport, A. P., Sarkodee-Adoo, C., Takebe, N., ... Flomenberg, N. (2004). Activity of single-agent melphalan 220-300 mg/m² with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma. Bone Marrow Transplantation, 33(8), 781-787. https://doi.org/10.1038/sj.bmt.1704424

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title = "Activity of single-agent melphalan 220-300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma",

abstract = "High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m2 plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D + 100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL + AF + AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D + 1163 (range D + 824 to D + 1630); one of these patients had a nonmyeloablative allograft as consolidation on D + 106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL + AF + AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.",

keywords = "Chemotherapy, Lymphoma, Stem cell transplantation cytoprotection",

author = "Phillips, {Gordon L.} and Meisenberg, {B. R.} and Reece, {D. E.} and Adams, {V. R.} and Badros, {A. Z.} and Brunner, {J. L.} and Fenton, {R. G.} and J. Filicko and Grosso, {D. L.} and Hale, {G. A.} and Howard, {D. S.} and Johnson, {V. P.} and A. Kniska and Marshall, {K. W.} and B. Mookerjee and R. Nath and Rapoport, {A. P.} and C. Sarkodee-Adoo and N. Takebe and Vesole, {D. H.} and Wagner, {J. L.} and N. Flomenberg",

note = "Funding Information: We thank our patients for their willingness to undergo clinical research studies; our nursing colleagues for their excellent patient care; our medical consultants for their valuable assistance; our data coordinators, and Ms M Coddington, Ms Lynn Stull and Ms Linda Wilkinson for their expert help with manuscript preparation. Finally, we thank Dr J Friedberg for his helpful suggestions with the manuscript. Grant support for this study was provided by the NIH, RO3CA80666 and ALZA.",

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doi = "10.1038/sj.bmt.1704424",

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Phillips, GL, Meisenberg, BR, Reece, DE, Adams, VR, Badros, AZ, Brunner, JL, Fenton, RG, Filicko, J, Grosso, DL, Hale, GA, Howard, DS, Johnson, VP, Kniska, A, Marshall, KW, Mookerjee, B, Nath, R, Rapoport, AP, Sarkodee-Adoo, C, Takebe, N, Vesole, DH, Wagner, JL & Flomenberg, N 2004, 'Activity of single-agent melphalan 220-300 mg/m² with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma', Bone Marrow Transplantation, vol. 33, no. 8, pp. 781-787. https://doi.org/10.1038/sj.bmt.1704424

TY - JOUR

T1 - Activity of single-agent melphalan 220-300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma

AU - Phillips, Gordon L.

AU - Meisenberg, B. R.

AU - Reece, D. E.

AU - Adams, V. R.

AU - Badros, A. Z.

AU - Brunner, J. L.

AU - Fenton, R. G.

AU - Filicko, J.

AU - Grosso, D. L.

AU - Hale, G. A.

AU - Howard, D. S.

AU - Johnson, V. P.

AU - Kniska, A.

AU - Marshall, K. W.

AU - Mookerjee, B.

AU - Nath, R.

AU - Rapoport, A. P.

AU - Sarkodee-Adoo, C.

AU - Takebe, N.

AU - Vesole, D. H.

AU - Wagner, J. L.

AU - Flomenberg, N.

N1 - Funding Information: We thank our patients for their willingness to undergo clinical research studies; our nursing colleagues for their excellent patient care; our medical consultants for their valuable assistance; our data coordinators, and Ms M Coddington, Ms Lynn Stull and Ms Linda Wilkinson for their expert help with manuscript preparation. Finally, we thank Dr J Friedberg for his helpful suggestions with the manuscript. Grant support for this study was provided by the NIH, RO3CA80666 and ALZA.

PY - 2004/4

Y1 - 2004/4

N2 - High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m2 plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D + 100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL + AF + AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D + 1163 (range D + 824 to D + 1630); one of these patients had a nonmyeloablative allograft as consolidation on D + 106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL + AF + AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.

AB - High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m2 plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D + 100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL + AF + AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D + 1163 (range D + 824 to D + 1630); one of these patients had a nonmyeloablative allograft as consolidation on D + 106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL + AF + AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.

KW - Chemotherapy

KW - Lymphoma

KW - Stem cell transplantation cytoprotection

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