Page 168 - 2019_02-Haematologica-web

C. Greil et al.
Table 2. Previous treatment and transplantation procedure. Remission state at allo-SCT n (%)
CR 13 (12) vgPR / PR 15 (14) / 27 (25) SD/MR 23(21)/1(1)
PD
Median number of prior treatment lines n (range) Pre-treatment with PI / IMID n (%)
Number of prior auto-SCT n (%)
30 (28)
3(1-8)
54 (50) / 47 (43)
0 9(8)
1
2
Median time between auto- and allo-SCT [months] (range) Median time between ID and allo-SCT [months] (range) Interval between auto- and allo-SCT n < / > 8 months
HLA compatibility n (%)
HLA-identical Related / syngeneic Unrelated
HLA-non-identical unrelated
Donor sex male / female n (%)
StemcellsourcePB/BMn(%) 108(99)/1(1) CMV-status n (%)
Donor positive /negative 49 (45) / 60 (55)
Patient positive / negative 67 (61) / 42 (39)
CR: complete remission; (vg)PR: (very good) partial remission; SD: stable disease; MR: minimal response; PD: progressive disease; PI: proteasome inhibitor; IMID: immunomodu- latory drug; auto-SCT: autologous stem cell transplantation; ID: initial diagnosis; allo-SCT: allogeneic stem cell transplantation; HLA: Human Leukocyte Antigen; PB: peripheral blood; BM: bone marow; CMV: cytomegalovirus.
74 (68)
26 (24) 17.3 (1.1 - 104.2) 27.7 (4.8 - 137.4) 47/53of100
92 (84) 43(39)/2(2) 47 (43)
17 (16)
71 (65) / 38 (35)
Methods
Patients’ description and data source
We retrospectively analyzed 109 consecutive patients diag- nosed with MM who had received RIC allo-SCT between 2000 and 2016 at the University Hospital of Freiburg. Data were ana- lyzed as of January 2018. Patient data were retrieved from our institution's electronic medical records. Depending on the aggres- siveness of their disease, patients received follow up on a regular basis. The analysis was carried out according to the Declaration of Helsinki and Good Clinical Practice guidelines. All patients gave their written informed consent for institutional-initiated research studies, approved by our institutional review board. Thirty-seven percent of our patients were treated in pre-emptive settings within different clinical trials of the German Myeloma Study Group (DSMM). Cytogenetic analysis was conducted in 82% of the patients. However, in 30%, FISH was only performed to detect the presence of deletion 13q14, an aberration that until recently was thought to be associated with shorter survival,22 and therefore had been implemented into the protocols of the DSMM and International Myeloma Working Group (IMWG) trials. Remission status was defined according to IMWG criteria.23 Relapse was defined as increase of serum paraprotein or occurrence of extramedullary disease. The Revised Myeloma Comorbidity Index (R-MCI) was determined as previously described.24,25 Karnofsky Performance Status (KPS), age, impairment of renal and lung function, frailty, and cytogenetic risk-group had been identi- fied as significant determinants for OS and were combined in a weighted score, allowing identification of fit (R-MCI 0-3), inter-
mediate-fit (R-MCI 4-6), and frail patients (R-MCI 6-9) with strik- ingly different median OS rates of 10.1, 4.4 and 1.2 years, respec- tively.24
Conditioning regimen and graft-versus-host disease prophylaxis
Patients were treated with different fludarabine-containing RIC regimens (Online Supplementary Table S1).
In almost all patients, stem cells were harvested from the peripheral blood; only one patient received bone marrow. Forty- one percent of all transplants were conducted with a related donor, 43% with an HLA-matched unrelated donor, and 16% with an HLA-mismatched unrelated donor. Allo-SCT was per- formed from a male versus female donor in 65% versus 35%, respectively (Table 2). Cyclosporin A was used for GvHD prophy- laxis, either in combination with alemtuzumab (37%) or mycophenolate mofetil (50%) or methotrexate (11%) with (41%) or without (59%) antithymocyte globulin (Online Supplementary Table S1).26
Statistical analysis
Data were analyzed using SAS statistical software version 9.4 (SAS Institute Inc., Cary, NC, USA). OS and PFS were calculated as time from allo-SCT to death from any cause and first observa- tion of relapse or death. NRM was defined as death without pro- gressive disease. Patients without observation of the event of interest at the last follow up were treated as censored observa- tions. OS and PFS rates were estimated and reported using the Kaplan-Meier method. Relapse and NRM were considered to be competing risks. Therefore, relapse and NRM rates were estimat-
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