High Dose Cyclophosphamide (HDCy) Post Stem Cell Transplant (SCT) Following High Dose Melphalan (HDMel) Based Conditioning As a Dual Strategy For Chemotherapy Dose Intensity and Graft Versus Host Disease (gvhd) Prophylaxis In Matched and Mismatched allogeneic (allo) SCT
Authors: Nath Rajneesh , Cerny Jan , Ramanathan Muthalagu , Raffel Glen D , Bednarik Jayde , Yu Neng , Desai Zankar , Shanahan Lindsey , Fortier Natasha , George Mridula , Kroll-Desrosiers Aimee 
Published: October 2019

Background
HDCy has been used post SCT in both haploidentical and matched sibling donor SCT for gvhd prophylaxis following non myeloablative conditioning as described by the John Hopkin's group. MD Anderson group (Ciurea et al: BBMT 18:1835-1844, 2012) has reported the feasibility of HDCy post a more intense HDMel based conditioning in haploidentical setting. There is no published data on the outcomes of this conditioning in matched and partially matched alloSCT.

Methods
We retrospectively analyzed the outcomes of all patients who HDMel based conditioning followed by HDCy post SCT at our institution.

Results
18 patients (12 males; 6 females) with a median age of 52 (range 25-70) years were identified from the database. Disease category was plasma cell malignancy (n=5); AML (n=4); ALL (n=4); MDS/MPD (n=3) and NHL/CLL (n=2). Nine patients had active disease at the time of SCT. One patient had a prior allogeneic SCT and 4 patients had prior auto SCT. Preparative regimen was fludarabine (25mg/m2 x5) HDMel (100-140 mg/m2) and thiotepa (5-10 mg/kg). One patient with lymphoma received Zevalin instead of thiotepa. HDCy (50mg/kg) was given on days 3 and 4 post SCT. HLA mismatched patients also received horse ATG (20mg/kg x 3). Additional gvhd prophylaxis was sirolimus in 14 patients and tacrolimus/mycophenolate in 4 patients.
Stem Cell source was peripheral blood in all patients. HLA matching was 10/10 in 11, 9/10 in 6 and 5/10 in one patient. 15 donors were unrelated and 3 were siblings. Median CD34 cells infused were 5.3 x 10e6/kg range (3.4 -7.5). All patients engrafted with a median time to neutrophil engraftment of 19 days (range 15-23) and a median time to platelet engraftment of 25.5 days (range 14-138). Cumulative incidence of grade 2-4 acute gvhd was 38.9% and chronic gvhd was 16.6%. Day 100, 6 month and 1 year survival was 100%, 87% and 80% (Figure 1). The median follow-up for survivors is 306.5 days (range 81-935). Four patients have died (hemopagocytic syndrome - day 187; progressive disease - day 455; persistent disease/gvhd - day 126; perforated bowel/gvhd - day 167). Ten (55%) patients were taken off all immune suppression at a median of 93 days (range 56-215) post SCT with an estimated cumulative incidence of immune suppression withdrawal of 73.2% (95% CI: 27.1-92.8) in 215 days (Figure 2).

Conclusion
HDCy post HDMel based conditioning is feasible in matched and partially matched allo SCT recipients with high risk hematological malignancies. This regimen delivers significant dose intensity and results in acceptable early mortality and high incidence of immunosuppression withdrawal early post SCT.

Disclosures:
Off Label Use: Most drugs in this study are off label for their use in stem cell transplant.