Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Provides Durable Progression-Free Survival (PFS) in a Subset of Diffuse Large B-Cell Lymphoma (DLBCL) Patients Relapsing after Autologous (auto-) HCT

Background: DLBCL relapsing after an auto-HCT has a poor prognosis. Unfortunately this is a common clinical dilemma, since ~50% of auto-HCTs for DLBCL ultimately fail. Allo-HCT is often considered following failure of an auto-HCT; however, limited information is available regarding prognostic factors identifying DLBCL patients likely to benefit from a subsequent allo-HCT. 

Methods: Adult (≥18 years) DLBCL patients undergoing an alloHCT between 2000-2012, after experiencing disease progression/relapse (P/R) following a prior autoHCT and reported to the CIBMTR were included. Patients undergoing tandem auto-allo HCT and those receiving allo-HCT for indications other than relapsed DLBCL were excluded. Primary outcomes were non-relapse mortality (NRM), P/R, PFS, and overall survival (OS). Cox regression method was used to develop a prognostic model of PFS and OS.

Results: Characteristics of 503 patients included in this analysis are shown in Table 1. The 3-yr univariate probabilities of NRM, P/R, PFS and OS were 30%, 38%, 31% and 37% respectively. Factors associated with higher NRM on multivariate analysis (MVA) included chemoresistance disease prior to allo-HCT (RR=1.86; p=0.003), myeloablative conditioning (MAC) (RR=1.99; p=0.0006; within 1^st 10months following alloHCT) and unrelated donors (URD) grafts (RR=1.44; p=0.03).  Factors associated with P/R on MVA included chemoresistance (RR= 2.25, p<0.0001), Karnofsky performance status (KPS) <80 (RR 1.81, p=0.006), and interval between auto-HCT and allo-HCT of <1 yr (RR=2.28, p<0.0001).  Factors associated with inferior PFS on MVA included KPS <80 (RR=1.79, p=0.0005), chemoresistance (RR=2.04, p<0.0001), auto-HCT to allo-HCT interval <1 yr (RR=1.32, p=0.01), and MAC (RR 1.29, p=0.03). Factors associated with worse OS on MVA included KPS <80 (RR1.86, p=0.0003), chemoresistance (RR=1.94, p<0.0001), MAC (RR=1.39, p=0.008). Three adverse prognostic factors were used to construct a prognostic model for PFS, including; (i) KPS <80 (2 points) (ii) Interval between auto-HCT & allo-HCT of <1yr (1 point) and (iii) chemoresistant disease at allo-HCT (2 points). This CIBMTR prognostic model classified patients into three prognostic groups: low risk (0-1 points), intermediate risk (2-3 points), or high risk  (4-5 points), predicting 3-yr PFS probabilities of 38% (95% CI=32-44), 19% (95% CI=11-27) and 10% (95% CI=0-22), respectively (Fig 1). The 3-yr OS probabilities in similar order were 43%, 25% and 14% respectively.

Conclusion: The CIBMTR prognostic model identifies a subgroup of DLBCL patients relapsing from an auto-HCT who can experience long-term PFS following an allo-HCT.   Reduced-intensity conditioning is preferred in this setting.

Table1	N=503 (%)
Median age at alloHCT, years	52 (range 19-72)
Male gender	305 (61)
KPS ≥80	393 (78)
Stage III-IV at diagnosis	54%
Rituximab prior to HCT	72%
Median lines of therapy	4 (range 1-7)
High LDH at HCT	34%
Time from auto-HCT to allo-HCT, months	15 (range 1-198)
Disease status at transplant
CR	175 (35)
PR	197 (39)
Chemorefractory	106 (21)
Untreated	12 (2)
Missing	13 (3)
Type of donor
Sibling	253 (50)
URD	250 (50)
Myeloablative conditioning	127 (25)
PB graft	456 (91)
TBI in conditioning	133 (26)
Median follow up, months	55 (range 1-149)