Haploidentical Allogeneic Hematopoietic Cell Transplantation for Mantle Cell Lymphoma Using Post-Transplantation Cyclophosphamide Graft-Versus-Host Disease Prophylaxis
Authors: De Philippis Chiara , Mariotti Jacopo , Bouabdallah Reda , Devillier Raynier , Bramanti Stefania , Harbi Samia , Furst Sabine , Legrand Faezeh , Sarina Barbara , Carlo-Stella Carmelo , Santoro Armando , Blaise Didier , Castagna Luca 
Published: October 2019

Abstract
Allogeneic Hematopoietic Cell Transplantation (allo-HCT) currently represents the only potentially curative therapy for patients affected by advanced Mantle Cell Lymphoma (MCL). Haploidentical HCT (haplo-HCT) allows virtually all patients to proceed to allo-HCT.
We analyzed survival outcomes of 20 MCL patients who received haplo-HCT at Humanitas Cancer Center and Institut Paoli Calmettes between 2012 and 2017. Median age of patients at transplant was 64 years (range, 35-71). Ten of them (50%) relapsed after autologous transplantation, one patient relapsed after allo-HCT (HLA identical sibling), while 9 underwent directly haplo-HCT due to the high risk of relapse (primary refractory disease). All patients except one had chemosensitive disease at transplant (75% complete response, 20% partial response, 5% progressive disease). In 10 patients, novel drugs were used as bridge to transplant to obtain response (8 patients were treated with ibrutinib, one with lenalidomide and one with bortezomib).
The hematopoietic-cell-transplantation comorbidity index (HCT-CI) was 0-1 in 4 patients, 2-3 in 12 patients and 4-5 in 4 of them. In 5 patients bone marrow was used as the source of stem cells, while the other 15 received peripheral blood stem cells. Sixteen patients received a nonmyeloablative conditioning regimen while 4 patients underwent a reduced intensity conditioning regimen. In all patients, post-transplant cyclophosphamide (PT-Cy) was used as graft-versus-host-disease (GVHD) prophylaxis.
Acute GVHD (aGVHD) was observed in 9 patients (grade I 2 patients, grade II 6 patients, grade III-IV 1 patient) at a median of 34 days from transplant (range, 21-80). The cumulative incidence of aGVHD grade 2-4 was 30% (95% CI, 12% to 51%) at 6 months. Three patients developed chronic GVHD (cGVHD) (1 mild, 1 moderate and 1 severe). The cumulative incidence at 2 years of moderate-severe cGVHD was 11% (95% CI, 2% to 30%).
With a median follow-up of 22 months (range 5-73 months), relapse or progression were observed in 2 patients at a median of 6 months (range, 3-8 months) from haplo-HCT with a cumulative incidence of disease relapse/progression of 11% (95% CI, 2% to 29%) at 3 years. The GVHD-free/relapse-free survival (GRFS) at 1 year was 68% (95% CI, 42% to 84%).
Three deaths were attributed to toxicity and occurred at a median of 123 days (range, 17-274 days) after transplant. The specific causes of death were: aGVHD, 1; infection, 1; cGVHD 1. The cumulative incidence of NRM was 16% (95% CI, 4% to 36%) at 3 years. The 3-years progression-free survival (PFS) and overall survival (OS) were 73% (95% CI, 47% to 88%) and 71% (95% CI, 43% to 77%), respectively.
Comparing this cohort with a similar cohort of 20 MCL patients who underwent allo-HCT from HLA identical sibling or unrelated donors in the same centers during the same time frame, the clinical outcomes (GRFS, NRM, PFS and OS) were not statistically different, even if there was a trend for better outcomes using haploidentical donor.
In conclusion, our study suggests that haplo-HCT with PT-Cy in MCL patients is feasible and is associated with a low relapse rate and NRM, even in the era of new drugs.
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Disclosures
Carlo-Stella: Bristol-Myers Squibb: Speakers Bureau; Sanofi: Consultancy; Genenta Science: Speakers Bureau; MSD Italia: Speakers Bureau; Janssen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau; AstraZeneca: Speakers Bureau; Amgen: Speakers Bureau; Boehringher Ingelheim Italia: Consultancy; Rhizen Pharmaceuticals: Research Funding.