330: Rituximab is Feasible to Administer to Allograft Recipients with Advanced CD20+ Malignancies and does not Affect Timely Hematopoietic Engraftment

M.A. Kharfan-Dabaja, C. Tate, J. Perkins, H.F. Fernandez, T. Field, E. Ayala, L. Perez, J. Raychaudhuri, M. Alsina, L. Ochoa-Bayona, D. Sullivan, L. Brand (+2 others)
2008 Biology of Blood and Marrow Transplantation  
range 0.2 -68 months) with 32% (12 patients) remaining alive at time of analysis. Sustained donor engraftment (neutrophils) occurred in 33 (89%) patients. The median time to neutrophil engraftment was 14 days (range 9-27); and for platelet engraftment 19 days (range 13-67). The median length of stay in hospital was 28 days (range 15-71). Twenty eight out of 37 patients (76%) were discharged from hospital post transplant. Nine patients (24%) required an Intensive Care admission. Seventeen out of
more » ... n. Seventeen out of the 37 patients (46%) had severe mucositis requiring opiates, with 6 requiring total parental nutrition. Graft vs Host Disease (GVHD) occurred in 24 individuals; 42% had acute GVHD (50% had .5 Grade 3 severity) and 55% had chronic GVHD (44% moderate to severe). The day 100 transplant-related mortality (TRM) was 32%, with the overall (all cause) mortality at 1 year of 51%. GVHD accounted for 6 (24%) deaths, primary disease 7 (28%) and sepsis 12 (48%). Conclusion: The combination of Fludarabine/Melphalan as a reduced intensity conditioning regime in this group of patients with advanced haematological malignancies can lead to prolonged disease control in up to one third of patients. However, it is not without its short term and long term toxicity, and is associated with a high day 100 transplant related mortality. A 40-year old female was diagnosed with stage II Hodgkin disease in 1998. She was treated with standard therapy, relapsed and underwent autologous stem cell transplantation (SCT). Two years later she developed primary CNS B cell diffuse large cell lymphoma, was treated, relapsed systemically and underwent a second autologus SCT. Two years later she relapsed again and received various therapies with partial response. In February 2006 she underwent matched unrelated donor (MUD) SCT with reduced intensity protocol containing fludarabine 200 mg/m 2 and melphalan 140 mg/m 2 . GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Donor (female) peripheral blood cells (7.7  10 6 CD34/kg) were collected in advance and cryopreserved. The cells were transferred to a smaller freezing tank 24 hours before the transplant. At the initiation of the transplant procedure the cells were found to be completely thawed due to leaking tank. The cells were infused and an aliquot was shown to have a viability of only 20%. The donor registry was contacted but the donor refused a further donation at that time. Hence, a second fully matched male donor was immediately located and a BM (1.74  10 6 CD34 cells/kg) was given, remarkably, 5 days following the first stem cell infusion. No additional chemotherapy or immunosuppression was given. Fourteen days following the 2 nd stem cell transplantation the patient developed diffuse erythematous rash, fever and watery diarrhea. Chimerism analysis (PCR for STR) revealed presence of both donors and no evidence of patient cells in peripheral blood (Table 1) . I.V. solumedrol (2 mg/kg) was started to treat a possible acute GVHD. Repeat analysis is described in [Table 1 ]. Unfortunately the patient remained neutropenic with no evidence for neutrophil and megakaryocyte precursors in BM. On day 42 from 1 st transplant the patient received CD34 positive stem cells boost (4.4  10 6 cells/kg) from the same first female donor, engrafted promptly after 7 days and became transfusion independent. GVHD was not aggravated following stem cell boost. The patient gradually stopped steroids and cyclosporine and remains alive and well after all immunosuppressive therapy. In conclusion, it appears that: (a) Low number of viable and thawed stem cells can survive and lead to engraftment. (b) Double allogeneic transplant ultimately leads to selection of a single donor as described for double cord-blood transplants. Allogeneic bone marrow transplantation (ALLO BMT) is a curative treatment for patients (pts) with acquired SAA. Current preparative therapies are associated with early and late sequelae such as organ injury, and secondary malignancies. We report the use of NMCR in patients with SAA. Patients and Methods: Four pts, ages 6-12 years, with SAA, had ALLO BMT from an HLA-identical sibling (SIB) (n 5 2) or a matched unrelated donor (MUD) (n 5 2). The reasons to offer NMCR were: delay in results of chromosome fragility studies, abnormal pulmonary function, history of recent life threatening infection, and failure to respond to immunosuppressive therapy. The NMCR consisted of fludarabine (FLU) (30 mg/m 2  4), low dose cyclophosphamide (LDC) (5 mg/kg  4) and rabbit antithymocyte globulin (rATG) (1.5 mg/kg  4) in patients with SIB donor and FLU, LDC, at 15 mg/kg  4, rATG and a single fraction of total body irradiation at 200 cGy in patients with a MUD donor. Results: The NMCR was well tolerated in all 4 patients. Two pts who had a SIB BMT had no transplant-related toxicities, including mucositis or alopecia. Toxicities in the MUD BMT pts included mild mucositis and partial alpecia in both pts. One pt (Pt#3) had reactivation od Enterobacter cloacae sepsis with typhlitis and later CMV viremia. Myeloid and platelet engraftment were uneventful in 3 pts. The recovery of peripheral blood counts was slow in Pt #3 following typhlitis and CMV viremia. Myeloid engraftment occurred on day 119 (range 15-33 days). The median time to a platelet count .20,000 unsupported by transfusion was day 133, (range 12-76 days). Periodic engraftmen anlyses using short tandem repeat (STR) by PCR continue to show full donor chimerism in all 4 pts. Acute GvHD of the skin was recorded only in the 2 pts with MUD BMT. One patient had limited chronic GvHD (Pt#3). Three pts. continue to do well with a fully recovered hematopoietic system at 44, 19 and 5 months post transplant, respectively. Pt #3 had a slow recovery of her peripheral counts but is transfusion independent for greater than 2 months and doing well 7 months post-transplant. Conclusion: This data suggests that a non-myeloablative, immunosuppressive regimen is sufficient to provide a stable engraftment in the patients with SAA. This approach may be associated with decreased transplant-related, short-and long-term, toxicities. A larger study is needed to fully evaluate the outcome and the toxicity associated with this conditioning. 330 RITUXIMAB IS FEASIBLE TO ADMINISTER TO ALLOGRAFT RECIPIENTS WITH ADVANCED CD201 MALIGNANCIES AND DOES NOT AFFECT TIMELY HEMATOPOIETIC ENGRAFTMENT 1st transplant Days from 2nd transplant Stem cell source Chimera 1st donor % Chimera 2nd donor % Fish Y chromosome %
doi:10.1016/j.bbmt.2007.12.340 fatcat:d553hcxnojfhdjgobgegbydh7i