The NCI Common Terminology Criteria for Adverse Events v3.0 is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.

High-dose melphalan at 200 mg/m 2 can be administered in 1 day or over 2 consecutive days before autologous hematopoietic cell transplantation (HCT) for multiple myeloma (MM). Limited data exist on the comparison of the two dosing schedules. A retrospective study of 278 consecutive MM patients receiving high-dose melphalan from January 2010 to December 2012 was conducted. Objectives were to compare the length of hospitalization, toxicity profile, response rates, PFS and OS. One hundred and eighty five patients received 2-day dosing and 93 received 1-day dosing. The two end points of the 95% confidence interval (CI) for the difference did not exceed the preselected margin, therefore the length of hospitalization was considered equivalent. No significant differences were found for response rates, PFS and OS. The toxicity profile was similar with the exception of more frequent ⩾ grade 3 oral mucositis in the 2-day group (13.5% vs 5.4%; odds ratio 3.07 (95% CI:1.11-8.48); P = 0.03). High-dose melphalan, given either in 1 day or over 2 days, produced comparable treatment outcomes except for increased grade 3/4 mucositis in the 2-day regimen. One-day dosing could shorten the hospital stay by 1 day and may allow better resource utilization. INTRODUCTIONMultiple myeloma (MM) is an incurable clonal B-cell neoplasm characterized by proliferation of malignant plasma cells in the BM, presence of monoclonal protein in the blood and/or urine and associated organ dysfunction. 1,2 MM comprises of~10% of all hematologic malignancies. OS of MM patients have steadily increased over the past few decades in part owing to the implementation of high-dose chemotherapy followed by autologous hematopoietic cell transplantation (HCT), availability of novel agents and improved supportive care. 3,4 Recent incorporation of lenalidomide to post-transplant maintenance therapy improved PFS, setting the stage for further incremental survival improvement. 5,6 Although high-dose melphalan 200 mg/m 2 is established as the standard conditioning regimen for autologous HCT, the practice variations exist on the dosing schedule. 7-9 High-dose melphalan can be administered over 1 day or given over 2 consecutive days (100 mg/m 2 /day). Adverse events deriving from high-dose melphalan occur in a dose-dependent fashion. Grazziutti et al. 10 found higher milligram per kilogram melphalan doses and renal dysfunction (both reflecting increased melphalan exposure) being the key pre-transplant factors for severe oral mucositis following autologous HCT in myeloma patients. Palumbo et al. 11 demonstrated a greater incidence of gastrointestinal side effects in patients with MM who received high-dose melphalan at 200 mg/m 2 vs patients who received melphalan 100 mg/m 2 as conditioning for tandem autologous HCT, where all doses of melphalan were given over 1 day. However, neither of the aforementioned studies compared toxicity profiles between

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative approach in patients with multiple myeloma, but its use for consolidation of first remission has not yet been fully explored. Twenty-two myeloma patients with very good partial response (VGPR) or CR received allogeneic peripheral blood grafts as consolidation from HLA-matched donors between 2007 and 2012. Conditioning regimens were fludarabine (30 mg/m2 i.v. if with bortezomib and 40 mg/m2 i.v. when without bortezomib, ×4 days) plus melphalan (70 mg/m2 intravenously ×2 days) with (n = 13) or without (n = 9) bortezomib (1.3 mg/m2). The cumulative incidence of grades 2–4 acute GVHD at day 100 was 45% (95% CI: 24–65%) and moderate-to-severe chronic GVHD at 2 years was 46% (95% CI: 19–69%). With a median follow-up of 18 (range, 2–61) months, the 2-year PFS estimate is 74.8% (95% CI: 45–90%), which compares favorably with the 52% (95% CI: 35–66%) after autologous HCT for similar patients (a median follow-up of 30 (range, 9–55) months). We are conducting a phase 2 study to assess the efficacy of allogeneic HCT as post-remission therapy.

Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n=293) to MTX/TAC (n=414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury. Day 100 grades II-IV acute GvHD was significantly reduced in SIR/TAC vs MTX/TAC group (63 vs 73%, P=0.02). An interaction between GvHD prophylaxis groups and comorbidity index (hematopoietic cell transplantation (HCT)-CI) significantly impacted OS. Patients with HCT-CI⩾4 had significantly worse OS with MTX/TAC (HR 1.86, 95% CI 1.14-3.04, P=0.01) while no such effect was seen for SIR/TAC (HR 0.78, 95% CI 0.48-1.26, P=0.31). Other end points did not significantly differ between groups except TMA and VOD/SOS were increased in the SIR/TAC group, but excess death from these complications was not observed. We conclude, GvHD prophylaxis approach of SIR/TAC is associated with reduced grades II-IV acute GvHD, comparable toxicity profile to MTX/TAC, and improved OS among patients with HCT-CI⩾4.

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