Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Multiple Myeloma

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Abstract

Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high nonrelapse mortality (NRM) rates, primarily from graft-versus-host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD after alloBMT. Here, we examine the impact of PTCy in patients with MM undergoing alloBMT at Johns Hopkins Hospital. From 2003 to 2011, 39 patients with MM underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning. Post-transplantation GVHD prophylaxis consisted of cyclophosphamide (50 mg/kg) on days +3 and +4 with or without mycophenolate mofetil and tacrolimus. Engraftment was detected in 95% of patients, with neutrophil and platelet recovery at a median of 15 and 16 days, respectively. The cumulative incidences of acute grades 2 to 4 and grades 3 and 4 GVHD were .41 and .08, respectively, and no cases of grade 4 acute GVHD were observed. The cumulative incidence of chronic GVHD was .13. One patient succumbed to NRM. All cases of chronic GVHD involved extensive disease and 60% of these patients received systemic therapy with complete resolution. After alloBMT, the overall response rate was 62% with complete, very good partial, and partial response rates of 26%, 21%, and 15%, respectively. The median progression-free survival was 12 months and was associated with the depth of response but not cytogenetic risk. The estimated cumulative incidence of relapse was .46 (95% confidence interval [CI], .3 to .62) at 1 year and .56 (95% CI, .41 to .72) at 2 years. At last follow-up, 23% of patients remain without evidence of disease at a median follow-up of 10.3 years after alloBMT. The median overall survival was 4.4 years and the 5-year and 10-year overall survival probabilities were 49% (95% CI, 35% to 67%) and 43% (95% CI, 29% to 62%), respectively. The use of PTCy after alloBMT for MM is feasible and results in low NRM and GVHD rates. The safety of this approach may allow the development of novel post-transplantation maintenance strategies to improve long-term disease control.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - 2017

Fingerprint

Graft vs Host Disease
Multiple Myeloma
Cyclophosphamide
Transplantation
Bone Marrow
Confidence Intervals
Mortality
Incidence
Tacrolimus
Cytogenetics
Disease-Free Survival
Neutrophils
Blood Platelets
Safety
Recurrence

Keywords

  • Allogeneic hematopoietic transplantation
  • Multiple myeloma
  • Post-transplantation cyclophosphamide

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{8e7a5bbc45c64bd6afdd816bf98ec3ac,
title = "Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Multiple Myeloma",
abstract = "Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high nonrelapse mortality (NRM) rates, primarily from graft-versus-host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD after alloBMT. Here, we examine the impact of PTCy in patients with MM undergoing alloBMT at Johns Hopkins Hospital. From 2003 to 2011, 39 patients with MM underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning. Post-transplantation GVHD prophylaxis consisted of cyclophosphamide (50 mg/kg) on days +3 and +4 with or without mycophenolate mofetil and tacrolimus. Engraftment was detected in 95% of patients, with neutrophil and platelet recovery at a median of 15 and 16 days, respectively. The cumulative incidences of acute grades 2 to 4 and grades 3 and 4 GVHD were .41 and .08, respectively, and no cases of grade 4 acute GVHD were observed. The cumulative incidence of chronic GVHD was .13. One patient succumbed to NRM. All cases of chronic GVHD involved extensive disease and 60% of these patients received systemic therapy with complete resolution. After alloBMT, the overall response rate was 62% with complete, very good partial, and partial response rates of 26%, 21%, and 15%, respectively. The median progression-free survival was 12 months and was associated with the depth of response but not cytogenetic risk. The estimated cumulative incidence of relapse was .46 (95% confidence interval [CI], .3 to .62) at 1 year and .56 (95% CI, .41 to .72) at 2 years. At last follow-up, 23% of patients remain without evidence of disease at a median follow-up of 10.3 years after alloBMT. The median overall survival was 4.4 years and the 5-year and 10-year overall survival probabilities were 49% (95% CI, 35% to 67%) and 43% (95% CI, 29% to 62%), respectively. The use of PTCy after alloBMT for MM is feasible and results in low NRM and GVHD rates. The safety of this approach may allow the development of novel post-transplantation maintenance strategies to improve long-term disease control.",
keywords = "Allogeneic hematopoietic transplantation, Multiple myeloma, Post-transplantation cyclophosphamide",
author = "Nilanjan Ghosh and Xiaobu Ye and Tsai, {Hua Ling} and Javier Bolaños-Meade and Fuchs, {Ephraim J.} and Leo Luznik and Swinnen, {Lode J.} and Gladstone, {Douglas E.} and Ambinder, {Richard F.} and Ravi Varadhan and Satish Shanbhag and Brodsky, {Robert A.} and Borrello, {Ivan M.} and Jones, {Richard J.} and William Matsui and Huff, {Carol Ann}",
year = "2017",
doi = "10.1016/j.bbmt.2017.07.003",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Multiple Myeloma

AU - Ghosh,Nilanjan

AU - Ye,Xiaobu

AU - Tsai,Hua Ling

AU - Bolaños-Meade,Javier

AU - Fuchs,Ephraim J.

AU - Luznik,Leo

AU - Swinnen,Lode J.

AU - Gladstone,Douglas E.

AU - Ambinder,Richard F.

AU - Varadhan,Ravi

AU - Shanbhag,Satish

AU - Brodsky,Robert A.

AU - Borrello,Ivan M.

AU - Jones,Richard J.

AU - Matsui,William

AU - Huff,Carol Ann

PY - 2017

Y1 - 2017

N2 - Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high nonrelapse mortality (NRM) rates, primarily from graft-versus-host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD after alloBMT. Here, we examine the impact of PTCy in patients with MM undergoing alloBMT at Johns Hopkins Hospital. From 2003 to 2011, 39 patients with MM underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning. Post-transplantation GVHD prophylaxis consisted of cyclophosphamide (50 mg/kg) on days +3 and +4 with or without mycophenolate mofetil and tacrolimus. Engraftment was detected in 95% of patients, with neutrophil and platelet recovery at a median of 15 and 16 days, respectively. The cumulative incidences of acute grades 2 to 4 and grades 3 and 4 GVHD were .41 and .08, respectively, and no cases of grade 4 acute GVHD were observed. The cumulative incidence of chronic GVHD was .13. One patient succumbed to NRM. All cases of chronic GVHD involved extensive disease and 60% of these patients received systemic therapy with complete resolution. After alloBMT, the overall response rate was 62% with complete, very good partial, and partial response rates of 26%, 21%, and 15%, respectively. The median progression-free survival was 12 months and was associated with the depth of response but not cytogenetic risk. The estimated cumulative incidence of relapse was .46 (95% confidence interval [CI], .3 to .62) at 1 year and .56 (95% CI, .41 to .72) at 2 years. At last follow-up, 23% of patients remain without evidence of disease at a median follow-up of 10.3 years after alloBMT. The median overall survival was 4.4 years and the 5-year and 10-year overall survival probabilities were 49% (95% CI, 35% to 67%) and 43% (95% CI, 29% to 62%), respectively. The use of PTCy after alloBMT for MM is feasible and results in low NRM and GVHD rates. The safety of this approach may allow the development of novel post-transplantation maintenance strategies to improve long-term disease control.

AB - Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high nonrelapse mortality (NRM) rates, primarily from graft-versus-host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD after alloBMT. Here, we examine the impact of PTCy in patients with MM undergoing alloBMT at Johns Hopkins Hospital. From 2003 to 2011, 39 patients with MM underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning. Post-transplantation GVHD prophylaxis consisted of cyclophosphamide (50 mg/kg) on days +3 and +4 with or without mycophenolate mofetil and tacrolimus. Engraftment was detected in 95% of patients, with neutrophil and platelet recovery at a median of 15 and 16 days, respectively. The cumulative incidences of acute grades 2 to 4 and grades 3 and 4 GVHD were .41 and .08, respectively, and no cases of grade 4 acute GVHD were observed. The cumulative incidence of chronic GVHD was .13. One patient succumbed to NRM. All cases of chronic GVHD involved extensive disease and 60% of these patients received systemic therapy with complete resolution. After alloBMT, the overall response rate was 62% with complete, very good partial, and partial response rates of 26%, 21%, and 15%, respectively. The median progression-free survival was 12 months and was associated with the depth of response but not cytogenetic risk. The estimated cumulative incidence of relapse was .46 (95% confidence interval [CI], .3 to .62) at 1 year and .56 (95% CI, .41 to .72) at 2 years. At last follow-up, 23% of patients remain without evidence of disease at a median follow-up of 10.3 years after alloBMT. The median overall survival was 4.4 years and the 5-year and 10-year overall survival probabilities were 49% (95% CI, 35% to 67%) and 43% (95% CI, 29% to 62%), respectively. The use of PTCy after alloBMT for MM is feasible and results in low NRM and GVHD rates. The safety of this approach may allow the development of novel post-transplantation maintenance strategies to improve long-term disease control.

KW - Allogeneic hematopoietic transplantation

KW - Multiple myeloma

KW - Post-transplantation cyclophosphamide

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U2 - 10.1016/j.bbmt.2017.07.003

DO - 10.1016/j.bbmt.2017.07.003

M3 - Article

JO - Biology of Blood and Marrow Transplantation

T2 - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

ER -