Melphalan at a dose of 200 mg/m2 is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m2 and melphalan 140 mg/m2 are equally effective and tolerable in clinically relevant patient subgroups we analyzed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 mg/m2 (n=245) and melphalan 200 mg/m2 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 mg/m2 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 mg/m2 versus melphalan 140 mg/m2: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favored melphalan 140 mg/m2 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 mg/m2 and melphalan 140 mg/m2 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favor the use of melphalan 200 mg/m2 or melphalan 140 mg/m2 for key transplant outcomes (NCT01362972).

JAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n = 274) or with (n = 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p = 0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p = 0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p = 0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age > 58 years (p = 0.03) and HLA mismatch donor (p = 0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.

We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti‐thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14‐0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35‐0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.

The advent of novel agents for multiple myeloma (MM) is cause for a re-examination of the incidence of second primary malignancies (SPMs). We examined the SPM rate in MM patients who were enrolled in the prospective observational CALM (Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma) study. Between 2008 and 2012, 3204 patients with MM underwent a first autologous hematopoietic stem cell transplantation. Plerixafor was used as a mobilizing agent for patients with poor (or potentially poor) stem cell mobilization as defined by the respective centers. A total of 135 patients developed SPMs, with a cumulative incidence of 5.3% (95% confidence interval, 4.4 to 6.3) at 72 months. Ninety-four patients developed solid tumors, 30 developed hematologic malignancies, and 11 developed an SPM of an unknown type. The cumulative incidence of known hematologic and solid malignancies were 1.4% and 3.6%, respectively, at 72 months. In a univariate analysis, use of radiotherapy, type of induction regimen, hematopoietic stem cell dose, poor mobilizer status, plerixafor use, and sex did not influence the cumulative incidence of SPMs. Only age over 65 years was statistically associated with an increased incidence. Overall, the incidence of SPMs was comparable to earlier estimations of SPMs in MM.

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