Role of Second Stem Cell Transplantation in Relapsed Lymphoproliferative Diseases: Remission Status Is the Most Important Factor Predicting the Outcome
Authors: Gil Lidia , Styczynski Jan , Piekarska Agnieszka , Jakubas Beata , Drabko Katarzyna , Wrobel Tomasz , Czyz Anna , Lojko-Dankowska Anna , Dytfeld Dominik , Nowicki Adam , Mensah-Glanowska Patrycja , Knopinska-Posluszny Wanda , Bieniaszewska Maria , Wysocki Mariusz , Hellmann Andrzej , Skotnicki Aleksander , Kowalczyk Jerzy , Kuliczkowski Kazimierz , Komarnicki Mieczyslaw 
Published: October 2019

Abstract
Abstract 3109
The outcome of patients (pts) relapsing after stem cell transplantation (SCT) is poor with limited therapeutic approaches in this group. A second or subsequent SCT is an option, however both high treatment related mortality (TRM) and high rate of disease relapse have been reported after such procedure so far. The objective of the study was to determine efficacy and safety of allogeneic SCT in patients relapsing with lymphoproliferative diseases after prior alloSCT or autoSCT.

Material and methods.
Fifty pediatric and adult patients with Hodgkin lymphoma (HL-24), non-Hodgkin lymphoma (NHL-10), acute lymphoblastic leukemia (ALL-9) and multiple myeloma (MM-7) in median age 33.5 (range: 3–56) years were included into the study. Nine pts relapsed after previous alloSCT and 41 after autologous transplant. The median time interval between previous transplant and relapse and median time interval between transplants were 8 (range :1–45) and 19 (range: 3–89) months, respectively. Complete remission (CR) was achieved in 23 pts before current transplant, while remaining 27 pts undergone alloSCT with active disease. For conditioning, reduced intensity protocols based on fludarabine were used in 46 pts, 4 were treated with myeloblative therapy based on total body irradiation (TBI). Stem cells from sibling (27) or unrelated (23) donors were grafted in median dose 4.1 (1.5–12.4)x10e6 of CD34+ cells/kg.

Results:
Engraftment was observed in 44 (88%) pts, 6 pts died before +21 day after transplant. Severe toxic complication (CTCAE grade 3–4) developed in 13 (26%) pts with multiorgan failure (MOF) in 7 of them. Infectious complications were observed in 41 (82%) pts (febrile of unknown origin 25, bacterial 10, fungal 3, bacterial+fungal 3). Acute graft versus host disease (GVHD) 2–4 grade occurred in 19 (38%) pts, while chronic extensive GVHD in 10 (20%) pts. Fifteen (30%) patients relapsed after treatment.
Over a median follow–up duration of 7 (range: 0–83) months, 19 (38%) pts were alive with median survival 25 (95%CI=14.5–35) months. Probability of 3-years overall survival (pOS) was 0.117±0.091. Among 31 (62%) pts who died, 11 early deaths (before +100 day post transplant) occurred: 4 due to infection and 7 because of MOF. Late deaths were caused by relapse (9), GVHD (7), toxicity (2) and infections (2). TRM was 44%.
The only factor contributing to 3-year pOS was remission vs active disease before transplant (0.458±0.140 vs 0.085±0.073; p=0.006). CR before second transplant reduced 2.9-fold (95%CI=1.3–6.2, p=0.008) the risk of death after procedure. Other estimated factors for OS (age, type of first transplant, pts and donor gender, conditioning method, stem cell source, toxic and infectious complications, GVHD occurrence, interval time between relapse and second transplant and between transplants) by Kaplan-Meier method were not statistically significant. Patients with late relapse (>6 months) after previous transplant reached survival plateau at 2 years (pOS=0.364±0.095 vs 0.0; ns).

Conclusions:
allogeneic SCT as a second procedure may be an option in relapsing patients with lymphoproliferative diseases after previous SCT. Remission status at time of salvage transplant is the most important determinant for the outcome. High rate of TRM remains a concern.

Disclosures:
No relevant conflicts of interest to declare.