Outcome of Hodgkin's Lymphoma Patients After Reduced-Intensity Allogeneic Stem Cell Transplantation: Complete Remission Status Has the Most Relevant Clinical Impact along with Extranodal Disease and C-Reactive Protein Before Transplant
Authors: Farina Lucia , Spina Francesco , Dodero Anna , Viviani Simonetta , Montefusco Vittorio , Milani Raffaella , Dalto Serena , Mariotti Jacopo , Carlo-Stella Carmelo , Corradini Paolo 
Published: October 2019

Abstract
Abstract 3542
Patients affected by Hodgkin's lymphoma (HL) who are chemorecfractory or relapsed after an autologous transplantation (autoSCT) may be eligible to a reduced intensity allogeneic stem cell transplantation (RIC alloSCT). Patients in progressive (PD) or stable disease (SD) at transplant seem to do worse than those in complete (CR) or partial remission (PR). We reviewed 43 cases of HL patients treated with a RIC alloSCT in our Institute from 2001 to 2010, focusing on the outcome based on disease status, disease characteristics, and treatment used to induce remission before transplant. Thirty patients (70%) were affected by nodular sclerosis HL. Median age at transplant was 31 (range, 53-19), 22 patients (51%) were female. The median number of previous chemotherapy was 4 (range, 2–10). Seven patients (16%) underwent autoSCT followed by alloSCT and 3/7 of them (43%) were in CR before allografting. All but one of the other 36 patients (81%) relapsed after an autoSCT and before allografting, were treated as follows: 19 received hyperfractioned polichemotherapy (D-PACE n=16, HypercHidam n=2, EPOCH n=1), 8 patients received conventional chemotherapy (gemcytabin based-chemotherapy n=4, BEACOPP n=1, bendamustine n=2, mecloretamin n=1) and 12/27 (44%) of these patients achieved CR, 8 patients received non-chemotherapy drugs alone or combined with chemotherapy in the setting of phase I-II trials and 3/8 (37%) were in CR at transplant, only one patient was in untested relapse. Thirty two (74%) patients had previously received radiotherapy. Disease status at transplant was: CR n=18 (42%), PR n=16 (37%), PD/SD n=9 (21%). Sixteen patients (37%) had extranodal disease. C-reactive protein (PCR) value at admission was above the normal range in 14 patients (33%). In 40 patients HCT-CI was assessed and it was 0 in n= 5 (13%), 1–2 n= 11 (27%), and ≥3 n= 24 (60%), with almost all the patients having abnormal pulmonary function tests. The type of donor was: HLA identical sibling n= 15 (35%), haploidentical sibling, n= 16 (37%), matched unrelated (MUD) n= 12 (28%). The conditioning regimen was based on thiotepa, fludarabine and cyclophosphamide; 2Gy TBI and T-cell depletion with alemtuzumab or ATG were used in case of haploidentical donor. The median follow-up of living patients was 26 months (range, 2–70).
All but one patients engrafted. The median PFS and OS were 10 months and 38 months, respectively. The estimated 3-year progression free survival (PFS) and 3-year overall survival (OS) were 37% and 52%, respectively. One year and 2-year transplant related mortality (TRM) was 7.6% and 10.8%, respectively. We performed an univariate analysis based on sex, histology, donor type (sibling versus MUD versus haploidentical), number of previous therapies (<=3 versus >3), extranodal disease, disease status before transplant (CR versus PR versus SD/PD), treatment received at relapse before alloSCT (chemotherapy versus autoSCT versus experimental drugs), previous radiotherapy, HCT-CI (0 versus ≥1), PCR value (normal versus abnormal). OS was influenced by sex (p=0.008, female patients did worse), disease status before alloSCT (p=0.025, both PR and PD/SD patients did worse than CR patients), extranodal disease (p=0.001), and elevated PCR (p=0.002). PFS was adversely correlated to female sex (p= 0.009), PR/PD/SD (p=0.0001), HCT-CI >=1 (p=0.03), extranodal disease (p=0.01), and abnormal PCR (p< 0.001). Haploidentical recipients showed a lower cumulative incidence of relapse (p=0.05), despite a higher NRM (0.02). Of note, the type of therapy received before transplant, either chemotherapy, autoSCT or experimental drugs, did not influence the outcome. In multivariate analysis including disease status, PCR value and extranodal disease, the latter was predictive of OS (p=0.04), disease status (CR versus PR/PD/SD) (p<0.001) and PCR value (p<0.01) were independent prognostic factors for PFS. PFS of patients with chronic graft-versus-host disease was not different compared to those without (p=0.29).
In conclusion, RIC alloSCT may be a feasible and efficacious treatment option in chemorefractory and relapsed HL patients, but CR status has been confirmed as one of the strongest predictor of outcome independently of the therapy used to achieve the response. An abnormal PCR value at the time of admission for transplant and a history of extranodal disease are also adverse prognostic factors.

Disclosures:
No relevant conflicts of interest to declare.