Abstract
Relapse of malignancy remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation. We have previously published our center experience showing that patients who relapse after haplo had a worse 1 year post-relapse survival (PRS) compared to relapses after matched related or unrelated donors (17%, 46% and 40% respectively , p<0.05)(Solh et al, BMT 2016). We hypothesized at that time that relative lack of donor lymphocyte infusion (DLI) use following haplo relapses could have contributed to the difference in outcomes between donor types, and commenced incorporation of DLI into the management strategy for relapse after haplo transplantation. To assess this hypothesis, we investigated the post-relapse survival among consecutive 392 patients who received their haplo transplant at our center between January of 2008 and January of 2020 and assessed for factors contributing to improved PRS.
Methods: A total of 392 patients who received their first haplo at our center were included in this analysis. Patient, disease, and transplant related factors were retrieved from our data base where they were prospectively entered. All transplants were performed in the outpatient setting with admissions reserved for complications that required inpatient care. GVHD prophylaxis for all patients was tacrolimus (till day 180), mycophenolate (stop at day 35) and cyclophosphamide 50mg/kg on days 3 and 4. Supportive care and GVHD management were per our programmatic standards. Endpoints included OS, DFS, NRM, relapse and post-relapse survival was assessed as survival from time of relapse. A landmark analysis for patients surviving more than 4 months post haplo was performed to assess for treatment factors affecting long term survival.
Results: out of 392 transplant recipients, 109 experienced relapse of malignancy after receiving their first haplo transplant with a median time from transplant to relapse of 194 days (range 43-1268) and median age at relapse of 53 years (20, 74). The patient characteristics for relapsing patients were as follows: diagnosis (AML 37%, ALL 21%, MDS 20%, Lymphoma 16%), prior auto (16%), HCT-CI 0-2 (45%), Disease risk (high/very high 51%). Transplant characteristics included myeloablative regimen (42%), peripheral blood cell source (75%), HLA match (5/10 in 72%, 6/10 in 16%, 7/10 in 12%), and female donor -male recipient in 23%. Post relapse remission induction with disease specific therapy was given to 102 out of 109 patients. Additionally, seventeen patients received DLI (cell dose (1x10 5 to 5x10 6 CD3+ cells/kg)and 10 patients received a second transplant post relapse. 3 patients developed GVHD (aGCVD 2, moderate severe cGHVD 1) after DLI infusion. 1 year and 3-year endpoints for the whole 392 patients were OS (79% and 63%), DFS (70% and 56%), NRM (11% and 15%) and relapse (19% and 29%). 1-year and 3-year post-relapse survival were 37% and 19%. IN a landmark analysis at 4 months, receiving DLI had significantly better OS than no DLI p=0.015(figure 1). On a multivariable analysis for OS, factors associated with improved OS included time from transplant to relapse (>=1 year vs <6 months, HR 0.29, 95% CI 0.16-0.54, p<0.001)), DLI ( yes versus no, HR 0.61, p=0.015)) and patient sex ( male vs female, HR 1.74, 95% CI 1.07-2.81, p=0.025).
In conclusion, some patients who relapse after Haplo with PTCY can still achieve long term remissions. The use of DLI in our experience is safe and contributed to improved survival. DLI should be considered in relapse management of haplo recipients.
Solh: Partner Therapeutics: Research Funding; BMS: Consultancy; ADCT Therapeutics: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy.
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