Outpatient Non-Myeloablative Allogeneic Stem Cell Transplantation For Myeloma Is Feasible, Efficacious and Associated With Low Transplant-Related Morbidity and Mortality

Reduced intensity/non-myeloablative allogeneic haemopoietic stem cell transplantation (allo HSCT) for myeloma following a myeloablative autologous stem cell transplant (ASCT), is associated with lower TRM rates than myeloablative allografting and has the potential to induce long term disease control through the well documented graft-versus-myeloma effect. Continuing attempts to reduce the procedure-related toxicity as well as resource utilisation are likely to result in the use of curative tandem auto-allo earlier in the disease course. We retrospectively reviewed the outcomes of 33 outpatient tandem autologous/non-myeloblative (NMA) conditioning allo HSCT referred to our institution.

Between May 2008 and December 2012, 33 patients were referred for tandem auto-allo procedures. Patients were transplanted either upfront (n=18) as part of their initial management or as a deferred procedure (n=15), usually as salvage following an initial autograft followed by maintenance/consolidation. Patients were transplanted upfront if they had one or more of the following high risk features: t(4;14) or t(14;16) translocations, 1q amplification, 1p and 17p deletion on cytogenetics/FISH; elevated LDH; stage III ISS disease or less than a PR with a novel agent-containing induction regimen. Patients were eligible for tandem auto-allo if they had achieved at least a PR to the latest therapy, had no significant co-morbidity and were less than 70 years of age. All autografts were conditioned with melphalan 200mg/m² and an outpatient NMA allo HSCT timed to occur 3 months later using oral fludarabine 48mg/m² on days -4 to -2 and 2Gy TBI on day 0 as conditioning. A target cell dose of 2 x 10⁶/kg CD34+ donor stem cells were infused on day 0. Graft versus host disease prophylaxis consisted of cyclosporine and mycophenolate mofetil.

The median age for the entire cohort was 52 (range 39-65), 19 males and 15 females and the median follow up was 719 days (50-1733). The overall response rate post-allo HSCT was 26/33 (79%) with a significantly higher proportion of CR/VGPRs seen in those transplanted upfront rather than deferred (15/18 v 7/15; p=0.03). The majority of patients were transplanted as outpatients (29/33) and only 4 were admitted for social reasons. Transplant complications requiring admission in the first 30 days occurred in 15/33 (45%) of patients, with a median length of stay of 1.5 days, and only 4 patients were hospitalised for more than 7 days. Median nadir neutrophil and platelet counts were 0.5 x 10⁹/L (range 0.1-1.1) and 94 x 10⁹/L ( range 23-143) respectively across the entire cohort and no patient experienced graft failure. Acute GVHD occurred in 14 (44%) of patients, was mild in the majority of cases and only 3 (9%) developing severe GII-IV aGVHD. Manageable chronic GVHD occurred in 19/31 (61%) evaluable patients, there were no transplant-related deaths by day 100 and 2 patients died of infection (microbiologically-unconfirmed sepsis at day 240 and disseminated nocardia infection at day 1025), resulting in a TRM of 6%. At the time of analysis, 26 (79%) patients were alive including 15 (45%) in ongoing CR. The median OS for the entire cohort has not been reached and the median PFS for all patients is 2.8years. Patients allografted upfront had significantly longer PFS compared to those recipients of a deferred transplant procedure (median NR versus 1.2 years respectively; p=0.03) but there was no significant difference in OS at 2 years follow up.

Tandem autologous/NMA allo HSCT for myeloma, when performed in the ambulatory setting, is feasible, well tolerated and associated with minimal toxicity and low TRM. Our results with outpatient tandem auto-allo compare favourably with ASCT and suggests allo HSCT may benefit selected patients earlier in their disease course.

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