Granulocytes for transfusion (GTX) continue to be administered, mostly to treat refractory infection 1. Single center series continue to be reported, but evidence of GTX effectiveness remains uncertain. Recent attempts at randomized trials of GTX have not been completed to target although the largest trial, RING 2, identified potentially promising results in a sub-group analysis by dose.
Abstract Introduction Reduced intensity (RIC) Alemtuzumab conditioned allogeneic stem cell transplants have enabled a successful graft versus leukaemia effect while GvHD rates were low. The impact of chimerism on outcome has scarcely been studied in RIC, Alemtuzumab-based transplants. Patient characteristics Retrospective analysis of 50 patients with high risk MDS (n=14) and AML (n=36) undergoing RIC-Alemtuzumab transplant in our center since 2006. Median age was 62 years (range 51-72) and there were 33 male and 17 female recipients. All donors were fully (10/10) matched in HLA-loci. 11 patients had a sibling donor while 39 had a matched unrelated donor. 29 patients were conditioned with fludarabine, melphalan and alemtuzumab while 21 patients received fludarabine, busulphan and alemtuzumab. Results The median follow-up of patients was 18.2 months (range 15-90). Median overall survival was 27.4 months and median progression free survival 33 months. At 3 months post-HSCT 72% (n=36) and 18% (n=9) of patients were full and mixed chimeras respectively. At 12 months post-HSCT n=19 and n=10 of patients were full and mixed donor respectively. 14 patients (28%) developed grade 1-2 GvHD while only 1 (2%) grade 3-4 GvHD. Patients who attained 12-month full donor chimerism in whole blood (WB), had a mean PFS of 85 months as compared to 81.5 months for mixed chimeras (p= 0.04). In 3-months, those who were full donor in WB had a mean PFS 95 months compared to 33 for mixed chimeras in WB (p= 0.016). 3, 12 -month T-cell chimerism did not influence OS and PFS. The presence of grade I-II GVHD was significantly associated with 12-month full donor chimerism in both WB and T-cells (p<0.05). Conclusion In our series of AML/MDS patients who received RIC Campath-based allografts, full donor chimerism is a surrogate marker for progression free and overall survival. All grade I/II aGVHD patients achieved full donor chimerism in whole blood. Disclosures Paneesha: Abvie: Honoraria. Kishore:celgene: Other: travel grant.
Abstract Introduction: Information is currently available for the efficacy and safety of autologous stem cell transplantation (ASCT) conditioned with melphalan in multiple myeloma patients with mild to moderate chronic kidney disease. However, little information is available on ASCT in patients with severe renal impairment or those on dialysis with multiple myeloma. This population is usually not considered for ASCT due to a high risk of mortality. One retrospective study provides data on ASCT conditioned mainly with 200mg/m2 melphalan with high treatment related mortality (TRM) at 15%. Here we present safety and efficacy data on dose reduced melphalan (140/m2) conditioned ASCT in patients with severe renal impairment or haemodialysis at the time of transplant with a TRM of 0%. Patients and methods: We identified and report on 10 ASCT procedures carried out on 9 (7 males and 2 females) myeloma patients with a glomerular filtration rate (eGFR) of 35 ml/min/1.73m2 or less between 2006 and 2016. Median age was 58(51-74) years. Five patients were on haemodialysis at diagnosis and 4 went into ASCT while on haemodialysis. Six patients had light chain multiple myeloma. Initial therapy was bortezomib based in 6 patients, with 4 receiving thalidomide and 1 received both thalidomide and bortezomib pre ASCT. Most patients were mobilised with G-CSF alone and only 1 received cyclophosphamide and G-CSF. ASCT was conditioned in all cases with 140mg/m2of Melphalan. Patients on hemofiltration were supported during ASCT as per institutional guidelines. We collected data on response, stem cell collection, engraftment, progression free survival (PFS), overall survival (OS) and treatment related mortality (TRM). Results: Median follow up for the whole group was 24 (6-114) months. Pre ASCT 6 patients were in VGPR and 3 in PR. The median cell dose collected was 6.92×10 6 CD34 cells/kg (range 3.06-8.27). The median time to neutrophil engraftment (absolute neutrophil count>0.5×109/L) and platelet engraftment (>20×109/L) was at day 13 and 15 respectively. The TRM at day+100 was 0%. Post ASCT best responses were as follows-7 patients were in VGPR; 1 in PR and 1 progressed. The median PFS was 24months and median OS was 27 months. At the time of data collection only one person had died. The cause of death was disease progression with refractory disease. One patient became free of haemodialysis pre ASCT, one after ASCT and 1 more dropped frequency of dialysis sessions from 3 to 2 per week. Discussion: Autologous stem cell transplant using low dose Melphalan (140mg/m2) as consolidation post a bortezomib based induction therapy is an effective and safe treatment option for the pre-dialysis and dialysis patients with multiple myeloma. In our hands the TRM is extremely low suggesting the lower dose to be more appropriate than melphalan at 200mg/m2. It provides good PFS and in some cases freedom from haemodialysis. Further prospective trials are needed to confirm these findings. Disclosures Paneesha: Abvie: Honoraria. Kishore:celgene: Other: travel grant.