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.
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.
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Joseph
J
Pidala
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.
Jaime
J
Roman-Diaz
Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.|Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA.
Jongphil
J
Kim
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.
Taiga
T
Nishihori
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.
Janelle
J
Perkins
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.
Cheryl
C
Tate
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Jose L
JL
Ochoa-Bayona
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.|Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA.
Teresa
T
Field
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Hugo F
HF
Fernandez
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Marcie
M
Tomblyn
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Ernesto
E
Ayala
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Claudio
C
Anasetti
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, 33612, USA. mk143@aub.edu.lb.|Department of Oncological Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA. mk143@aub.edu.lb.|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. mk143@aub.edu.lb.
Mohamed A
MA
Kharfan-Dabaja
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
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