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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

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Abstract

We examined pharmacokinetic-targeted IV busulfan (75–170 mg/m2, with target AUC of 3500–6000 μmol min) and fludarabine (40 mg/m2) × 4 days with rituximab (t-IV Bu/Flu + rituximab) 375 mg/m2 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/m2 to t-IV Bu/Flu does not appear to adversely affect engraftment, donor chimerism, or increase the risk of infectious complications.

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Conflict of interest

The authors report the following funding sources which have relevance to the work described here: Claudio Anasetti, MD, and Janelle Perkins, PharmD, have research funding from Protein Design Labs BioPharma for the conduct of research involving busulfan and fludarabine as conditioning therapy prior to allogeneic transplantation.

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Correspondence to Mohamed A. Kharfan-Dabaja.

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J. Pidala and J. Roman-Diaz contributed equally to this work.

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Pidala, J., Roman-Diaz, J., Kim, J. et al. 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 93, 206–212 (2011). https://doi.org/10.1007/s12185-010-0747-x

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  • DOI: https://doi.org/10.1007/s12185-010-0747-x

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