Nonmyeloablative allogeneic hematopoietic stem cell transplant for the treatment of patients with hematologic malignancies using busulfan, fludarabine, and total body irradiation conditioning is effective in an elderly and infirm population

Jonathan E. Brammer, Alexander Stentz, James Gajewski, Peter Curtin, Brandon Hayes-Lattin, Tibor Kovacsovics, Jose F. Leis, Gabrielle Meyers, Eneida Nemecek, Nan Subbiah, Rachel Frires, Gundula Palmbach, Galit Perets Avraham, Susan Slater, Richard Maziarz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day -5, fludarabine 30 mg/m2 IV on days -4, -3, -2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59% with myeloid disease and 41% with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60% at 1 year and 48% at 2 years, with projected OS 37% at 5 years. Relapse rates were 29% at 1 year and 33% at 2 years, with relapse mortality of 13% at 1 year, and 20% at 2 years. Nonrelapse mortality (NRM) at 1 year was 27% and 33% at 2 years. 54% of patients developed grade II-IV aGVHD and 67% of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.

Original languageEnglish (US)
Pages (from-to)89-96
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Busulfan
Whole-Body Irradiation
Hematologic Neoplasms
Hematopoietic Stem Cells
Transplants
Survival
Population
Mortality
Therapeutics
Mycophenolic Acid
Recurrence
Unrelated Donors
Cyclosporine
fludarabine
Comorbidity
Outpatients
Stem Cells
Blood Platelets
Multivariate Analysis
Neoplasms

Keywords

  • Comorbidity index
  • Elderly
  • Leukemia
  • Lymphoma
  • Nonmyeloablative
  • Stem cell transplantation

ASJC Scopus subject areas

  • Transplantation
  • Hematology
  • Medicine(all)

Cite this

Nonmyeloablative allogeneic hematopoietic stem cell transplant for the treatment of patients with hematologic malignancies using busulfan, fludarabine, and total body irradiation conditioning is effective in an elderly and infirm population. / Brammer, Jonathan E.; Stentz, Alexander; Gajewski, James; Curtin, Peter; Hayes-Lattin, Brandon; Kovacsovics, Tibor; Leis, Jose F.; Meyers, Gabrielle; Nemecek, Eneida; Subbiah, Nan; Frires, Rachel; Palmbach, Gundula; Avraham, Galit Perets; Slater, Susan; Maziarz, Richard.

In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 1, 01.01.2015, p. 89-96.

Research output: Contribution to journalArticle

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abstract = "The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day -5, fludarabine 30 mg/m2 IV on days -4, -3, -2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59{\%} with myeloid disease and 41{\%} with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60{\%} at 1 year and 48{\%} at 2 years, with projected OS 37{\%} at 5 years. Relapse rates were 29{\%} at 1 year and 33{\%} at 2 years, with relapse mortality of 13{\%} at 1 year, and 20{\%} at 2 years. Nonrelapse mortality (NRM) at 1 year was 27{\%} and 33{\%} at 2 years. 54{\%} of patients developed grade II-IV aGVHD and 67{\%} of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.",
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