Targeted IV busulfan and fludarabine followed by post-allogeneic hematopoietic cell transplantation rituximab demonstrate encouraging activity in CD20+ lymphoid malignancies without increased risk of infectious complications

Joseph Pidala; Jaime Roman-Diaz; Jongphil Kim; Taiga Nishihori; Janelle Perkins; Cheryl Tate; Jose L Ochoa-Bayona; Teresa Field; Hugo F Fernandez; Marcie Tomblyn; Ernesto Ayala; Claudio Anasetti; Mohamed A Kharfan-Dabaja

doi:10.1007/s12185-010-0747-x

Targeted IV busulfan and fludarabine followed by post-allogeneic hematopoietic cell transplantation rituximab demonstrate encouraging activity in CD20+ lymphoid malignancies without increased risk of infectious complications

Int J Hematol. 2011 Feb;93(2):206-212. doi: 10.1007/s12185-010-0747-x. Epub 2011 Jan 19.

Authors

Joseph Pidala^{1

2}, Jaime Roman-Diaz¹, Jongphil Kim^{2

3}, Taiga Nishihori¹, Janelle Perkins¹, Cheryl Tate¹, Jose L Ochoa-Bayona^{1

2}, Teresa Field^{1

2

3}, Hugo F Fernandez^{1

2}, Marcie Tomblyn^{1

2}, Ernesto Ayala^{1

2}, Claudio Anasetti^{1

2}, Mohamed A Kharfan-Dabaja^{4

5

6}

Affiliations

¹ Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.
² Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
³ Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA.
⁴ Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA. [email protected].
⁵ Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA. [email protected].
⁶ Division of Hematology-Oncology-BMT, Department of Internal Medicine, American University of Beirut, P.O. Box 11-0236, Riad El Solh, Beirut, 1107 2020, Lebanon. [email protected].

Abstract

We examined pharmacokinetic-targeted IV busulfan (75-170 mg/m(2), with target AUC of 3500-6000 μmol min) and fludarabine (40 mg/m(2)) × 4 days with rituximab (t-IV Bu/Flu + rituximab) 375 mg/m(2) on days +1 and +8 followed by allogeneic hematopoietic cell transplantation in 19 patients (median age 56, range 35-68 years) with CD20+ lymphoid malignancies. Median time to neutrophil and platelet engraftment was 15 and 12 days. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 58% (95% confidence interval, CI 39-85%), and chronic GVHD was 50% (95% CI 28-88%). With a median follow up of 7 (range 1-31) months, overall response was observed in 15, and stable or progressive disease in 4. Overall survival at 1 year was 67%. Engraftment, chimerism, and infectious complications did not differ significantly from a contemporaneous non-rituximab containing comparator group. The addition of rituximab 375 mg/m(2) to t-IV Bu/Flu does not appear to adversely affect engraftment, donor chimerism, or increase the risk of infectious complications.

Publication types

Comparative Study

MeSH terms

Adult
Aged
Antibodies, Monoclonal, Murine-Derived / administration & dosage
Antibodies, Monoclonal, Murine-Derived / adverse effects
Antibodies, Monoclonal, Murine-Derived / therapeutic use*
Antigens, CD20 / metabolism
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Busulfan / administration & dosage
Busulfan / adverse effects
Busulfan / therapeutic use*
Cohort Studies
Female
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Leukemia, Lymphoid / drug therapy*
Leukemia, Lymphoid / metabolism
Leukemia, Lymphoid / therapy
Lymphoma / drug therapy*
Lymphoma / metabolism
Lymphoma / therapy
Male
Middle Aged
Retrospective Studies
Rituximab
Transplantation Conditioning*
Vidarabine / administration & dosage
Vidarabine / adverse effects
Vidarabine / analogs & derivatives*
Vidarabine / therapeutic use

Substances

Antibodies, Monoclonal, Murine-Derived
Antigens, CD20
Antineoplastic Agents
Rituximab
Vidarabine
Busulfan
fludarabine

Grants and funding

P30 CA076292/CA/NCI NIH HHS/United States