Allogeneic Hematopoietic Cell Transplant Yields Long Term Disease Free Survival in a Significant Number of Patients with Classic Hodgkin Lymphoma

Background:

Classic Hodgkin's lymphoma (cHL) is a highly curable disease. A minority of patients, however, will have relapse/refractory (RR) disease and these patients are challenging to manage especially those who relapse after autologous hematopoietic cell transplant (auto-HCT). Even though a number of salvage options are available for these patients none of them is considered curative except allogeneic hematopoietic cell transplant (allo-HCT).

Design and Methods:

Retrospective analysis of 33 patients who had allo-HCT using matched family donors for cHL between January 2007 and December 2021. Continuous variables were summarized using medians and ranges. Categorical variables were summarized using frequencies and percentages. Probabilities of overall survival (OS) and disease free survival (DFS) were calculated using Kaplan-Meier estimate. Statistical analysis was conducted sing R studio (version 1.3.959 © 2009-2020 RStudio, PBC).

Results:

The median patient age at allo-HCT was 27 years. Seventeen patients were males and 16 were females. Five patients had early stage disease (Ann Arbor stage I, II) and 28 had advanced stage disease (Ann Arbor III, IV). Regarding the histologic type of cHL, eighteen had nodular sclerosis (NS), eight had mixed cellularity (MC), one had lymphocyte rich (LR), one had lymphocyte depleted (LD) and five cases were labeled as classic HL without further classification. Seventeen patients received brentuximab vedotin and fourteen patients received check point inhibitors prior to allo-HCT. The median number of chemotherapy lines prior to allo-HCT was 4 (range: 2-8). Twenty seven patients had chemosensitive disease (complete or partial remission) while 6 patients had chemoresistant disease (stable or progressive) prior to allo-HCT. Twenty seven patients had undergone auto-HCT prior to allo-HCT. Eighteen patients had elevated (>50) erythrocyte sedimentation rate (ESR) while 15 had normal ESR prior to allo-HCT. The majority of patients were conditioned with a reduced intensity regimen (29 patients versus 4 patients conditioned with myeloablative regimen). Twenty five patients received non-TBI (total body irradiation) based conditioning while 8 patients had TBI based regimen. The most frequently used conditioning regimen was fludarabine + melphalan. Nine patients received ATG (anti thymoglobulin) as a part of the conditioning while 24 patients did not. Thirty one patients received peripheral blood graft while 2 patients received bone marrow graft. The five years DFS was 37.5%. Twenty seven % of patients had acute GVHD (graft versus host disease) and 48% had chronic GVHD. The effect of a number of variables (number of chemotherapy lines, pre-allo-HCT ESR, conditioning intensity, ATG vs no ATG, receipt of pre-allo-HCT brentuximab or check point inhibitors, prior auto-HCT, chemosensitivity pre-allo-HCT and histologic subtype) was tested on the DFS. The only two variable that were statistically associated with a better DFS were pre-allo-HCT chemosensitivity (P=0.006) and non-NS histologic subtype (P=0.027). (Figure 1 and 2).

Conclusions:

Allogeneic stem cell transplantation can result in long-term progression-free survival in heavily pre-treated patients with Hodgkin's lymphoma. Patients with no response to salvage chemotherapy pre-allo-HCT and patients with NS subtype had detrimental outcomes. Better selection of patients before allo-HCT can result in a higher cure rates.

No relevant conflicts of interest to declare.