Haploidentical Stem Cell Transplantation in Patients Over Age 75‚ÄâYears Using Reduced Intensity Conditioning Chemotherapy and Post-transplant Cyclophosphamide Based GVHD Prophylaxis: A Report of Two Patients.

Introduction:
Haploidentical stem cell transplantation (Haplo SCT) is a curative option in patients with hematological malignancies. For patients older than age 70, SCT from matched donors (sibling/unrelated) has been reported in several studies. For patients lacking suitable matched donors there is only one report of haplo-SCT in patients over age 70 using post-transplant cyclophosphamide (PTCy) based GVHD prophylaxis using non myeloablative (NMA) conditioning. NMA conditioning is associated with a higher relapse rate compared to RIC. We report two patients older than age 75 with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) who underwent RIC haplo SCT with PTCy based GVHD prophylaxis.
Results:
. Prior history consisted of HPV associated rectal cancer in 2009 treated with chemoradiation. In 2019 she was diagnosed with RAEB-2. She received Decitabine x 4 cycles and achieved a morphologic and cytogenetic remission. HCT-CI score was 4. She underwent RIC conditioning (Thiotepa 1mg/kg, Fludarabine 30 mg/m2x5, Melphalan 70mg/m2 m2). GVHD prophylaxis consisted of PTCy (50mg/kg x2) days 3 &4, thymoglobulin 1mg/kg day 5 along with tacrolimus and sirolimus. She engrafted her neutrophils on day 16 and platelets on day 20 showing full donor chimerism in both blood and bone marrow. She did not have any GVHD. Azacitadine/venetoclax maintenance every 4-6‚Äâweeks was started on day 61. Patient had cytogenetic relapse 9-month post SCT. Immune suppression was stopped. Marrow at month 16 showed persistent monosomy 7 but it disappeared at month 22 post SCT. Patient is currently 30 months post haplo SCT with normal counts, gvhd free and off immunosuppression with good immune recovery (CD4 393 /uL; IGG 753 mg/DL). She continues aza/ven planned till 3‚Äâyears post SCT.

He presented in 03/17 with pancytopenia. Bone marrow revealed AML. He underwent induction chemotherapy followed by 3 cycles of decitabine. Repeat bone marrow biopsy revealed 5% leukemic blast. HCT-CI score was 2. He underwent RIC conditioning (Thiotepa 2.5 mg/kg, Fludarabine 30 mg/m2x5, Melphalan 60mg/m2). GVHD prophylaxis consisted of PTCy (50mg/kg x2) days 3 &4, thymoglobulin 1mg/kg day 5 along with tacrolimus and sirolimus. He engrafted neutrophils on day 19 and platelets on day 26. There was no acute of chronic GVHD. He received a single cycle of maintenance azacitadine on day 50 post-SCT. Day-100 and 7-month bone marrow exam revealed CR with normal cytogenetics and full donor chimerism. There was no GVHD, and he was taken off all immunosuppression on day 236 post SCT. Patient presented with thrombocytopenia at 9-month post SCT. Bone marrow showed cytogenetic relapse. He received one cycle of Decitabine/Venetoclax. The patient expired on day 369 post- SCT secondary to complications from a fall.
Discussion:
These two patients demonstrate the feasibility of using RIC conditioning in elderly patients undergoing haplo SCT with PTCy based GVHD prophylaxis. Additional studies are needed to better define the role of this strategy in elderly patients using both matched and mismatched donors.