Weight Loss, CD-34 Cell Dose and Melphalan Dose More Than 5 Mg/Kg Independently Predicted Severe Complications in Patients with Myeloma Undergoing Transplant.

Abstract 3145

Melphalan-based autologous stem cell transplant (Mel-ASCT) is effective therapy for multiple myeloma but can be associated with significant morbidity and life threatening complications. Developing pre-transplant predictors for severe complications is therefore of paramount importance.

Our objective was to identify independent predictors of severe complications following Mel-ASCT defined as hospitalizations for 7 or more days or death.

We reviewed the records of 190 patients with newly diagnosed multiple myeloma who underwent their first Mel-ASCT as part of our Total Therapy protocol (TT4). The treatment protocol randomized patients with low risk myeloma to receive standard therapy according to the predecessor trial TT-3 trial, or less intense therapy (light arm). Compared to the standard arm (TT4S), the light arm (TT4L) consisted of only one cycle of induction prior to Mel-ASCT compared to two for TT4S and reduced the melphalan dose to 140 mg/m² for serum creatinine >3mg/dl. The following baseline variables were examined: demographics, weight, CBC, pre-transplant albumin, renal and liver function tests, peripheral blood CD3 and CD4 counts, stem cell product CD34 dose, echocardiogram, pulmonary function tests and mg/kg melphalan dose received. Univariate and multivariate analyses for outcome predictors were performed.

190 patients (96 TT4S and 94 on TT4L) underwent their first Mel-ASCT November 2008 through July 2011. Median age was 58.2 years. One hundred and sixteen patients were males. Patients were followed up to 60 days post-transplant.

Severe complications for mortality occurred more commonly in the standard arm with 5 deaths than in the light arm with 1 death. Severe complications requiring hospital admission for more than seven days developed in 18 patients. Ten of these patients were in the standard arm and eight patients were in the light arm.

Predictors of unfavorable outcomes in the combined group by univariate analysis were weight loss greater than 5% during induction(p=0.0029), platelets less than 65 (p=0.0090), CD34 cells/kg (p=0.0429), Beta-2 microglobulin >3.5 (p=0.0054), high ALT (p=0.0456), low socioeconomic status (p=0.0050), and dose of melphalan greater than 5 mg of melphalan/kg (p=0.0346).

Only three of the variables in the univariate analysis were significant in the combined multivariate analysis. These three variables are presented in the table below.

We conclude that melphalan dose greater than 5 mg/kg, infusion of less than 3.5× 10⁶ CD34 cells/kg and greater than 5% loss of body weight during induction predict for severe complications during Mel-ASCT. Reducing intensity of induction therapy appears to be associated with less severe complications during Mel-ASCT.