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

• Published in: International journal of hematology 2011-02, Vol.93 (2), p.206-212
• Main Authors: Pidala, Joseph, Roman-Diaz, Jaime, Kim, Jongphil, Nishihori, Taiga, Perkins, Janelle, Tate, Cheryl, Ochoa-Bayona, Jose L., Field, Teresa, Fernandez, Hugo F., Tomblyn, Marcie, Ayala, Ernesto, Anasetti, Claudio, Kharfan-Dabaja, Mohamed A.
• Format: Article
• Language: English
• Subjects: 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; Biological and medical sciences; Busulfan - administration & dosage; Busulfan - adverse effects; Busulfan - therapeutic use; Cohort Studies; Female; Hematologic and hematopoietic diseases; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Leukemia, Lymphoid - drug therapy; Leukemia, Lymphoid - metabolism; Leukemia, Lymphoid - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma - drug therapy; Lymphoma - metabolism; Lymphoma - therapy; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Retrospective Studies; Rituximab; Transplantation Conditioning; Vidarabine - administration & dosage; Vidarabine - adverse effects; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-010-0747-x

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.