• Change in IPSS-R between diagnosis and transplant and transplant outcome in patients with MDS. a retrospective analysis from the chronic malignancies working party.

      Scheid, C.; Eikema, D. J.; Niittyvuopio, R.; Maertens, J.; Passweg, J.; Blaise, D.; Byrne, J.; Kroger, N.; Bornhauser, M.; Chevallier, P.; et al. (2021)
      Background: IPSS-R is a well established prognostic factor for transplant outcome in patients with MDS, irrespective whether it is assessed at diagnosis or at transplant. However it is unclear how a change in IPSS-R, e.g. by reducing bone marrow blasts through therapy, would potentially affect transplant results. In particular the decision to treat patients before transplant or perform an upfront allogeneic transplantation can so far not be based on evidence. Methods: From the EBMT registry patients with MDS and sufficient data to calculate IPSS-R at diagnosis and before transplant were identified from the period 2005 - 2018. 1482 patients were analysed. Median age was 59 (interquartile range 51-64) years, 60% were male, 40% female. Donors were related in 36% and unrelated in 64%, graft source was PBSC in 85% of cases. Conditioning was standard dose in 33% and reduced intensity in 67%. Results: IPSS-R both at diagnosis and at transplant had a significant impact on OS and RFS. To investigate the effect of a change in IPSS-R between diagnosis and transplant we formed 3 subgroups: same IPSS-R, improved IPSS-R, worsened IPSS-R. A change in IPSS-R was noted 77.5% of patients with prior chemotherapy, 72% with prior HMA and 59.8% of untreated patients. Univariate analysis showed no significant difference in OS or RFS in patients with stable IPSS-R compared to improved or worsened IPSS-R. To analyse the effect of a change in IPSS-R in the context of IPSS-R at diagnosis and type of therapy between diagnosis and transplant (none, chemotherapy, HMA, other) a multivariable Cox regression for OS and RFS was performed. From this model the predicted OS at 2yrs for untreated patients with high risk IPSS-R at transplant was 63%, 57% and 65% for same, improved or worsened IPSS-R, respectively. With chemotherapy predicted 2yr OS was 35%, 59% and 32%, with HMA 46%, 48% and 19%, with other treatments 2yr OS was 35%, 46% and 21% for same, improved or worsened IPSS-R. RFS at 2 years in patients with high-risk IPSS-R at diagnosis was predicted 55%, 49% and 57% with no treatment, 31%, 54% and 31% after chemotherapy, 41%, 40% and 14% after HMA, and 36%, 40% and 15% after other therapies. Similar results were obtained for the other IPSS-R risk categories. Conclusions: In this retrospective analysis from a large cohort of patients with MDS a change in IPSS-R between diagnosis and transplant did not appear to affect OS and RFS after transplant in patients with no intermittent treatment. In treated patients worsening of IPSS-R had a negative effect on OS and RFS. Improving IPSS-R after therapy however did not show a positive effect on OS or RFS. Thus for MDS patients receiving an allogeneic transplantation our results provide no clear signal that prior therapy improves transplant outcome.
    • Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party

      Hayden, P. J.; Eikema, D. J.; de Wreede, L. C.; Koster, L.; Kröger, N.; Einsele, H.; Minnema, M.; Dominietto, A.; Potter, M.; Passweg, J.; et al. (2021)
      The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.