Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center.

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach. Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting. Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18-44) underwent allo-SCT between 2002 and 2020. Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%. Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

The efficacy and safety of autologous stem cell transplantation in relapsed chemosensitive and chemoresistant patients with diffuse large B-cell lymphoma.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains a valuable therapeutic approach for relapsed and refractory (R/R) patients with diffuse large B-cell lymphoma (DLBCL). The aim of the study was to evaluate the safety and clinical outcome of ASCT for R/R DLBCL. We present a retrospective series of ASCT for 53 DLBCL patients (30 males and 23 females) at the median age of 51 years. Patients were eligible for transplantation if they achieved partial, second, or subsequent response or remained stable to at least 2 prior treatments. Median overall (OS) and progression-free (PFS) survivals were 9 and 6.3 years, respectively. The estimated 4-year OS and PFS were found to be 75% and 69%, respectively. In univariate analysis liver involvement, clinical stage at diagnosis, lymphocyte/monocyte count, and status of clinical response at ASCT were found to influence OS, however, only absolute lymphocyte count remained significant in multivariate analysis (HR 1.42 [95% CI: 1.08-1.87]; p=0.01). Median follow-up from ASCT to the last contact was 4.4 years (range 0.03-18.7). In total, 26 patients died from disease progression and subsequent resistance to chemotherapy. At the last contact, 27 patients were alive in remission. Only a single patient died shortly after ASCT due to infectious complications. Grade 3 or 4 non-hematological side effects were not observed in the remaining patients. ASCT for RR DLBCL is a safe procedure with a high probability of overall and progression-free survival.

Safety profile of a single pegylated asparaginase (PEG-ASP) dose in remission induction for acute lymphoblastic leukemia (ALL).

The incorporation of pegylated asparaginase (PEG-ASP) in pediatric and adult acute lymphoblastic leukemia (ALL) protocols remains a worldwide therapeutic approach. However the safety profile remains a challenge, and herein we report the toxicity of an intravenous single dose of 1000 IU/m2 PEG-ASP administered in remission induction for adult ALL patients. Thirty-two patients at median diagnostic age of 32 years (median of 19-65) were included in this analysis. Most patients had B-cell lymphoblastic leukemia (n=26; 78%) and 81% of cases were <55 years at study entry. 75% of patients had <30x109/l leukocyte count at diagnosis and median follow-up was 14 months (range 0.8-69). All grade 3/4 adverse events (AEs) after PEG-ASP administration were observed in 24 patients (75%). The most common grade 3/4 AEs were: decreased fibrinogen (58%), increased bilirubin (31%) and increased GGTP (27%). Clinical manifestations related to PEG-ASP were seen in 9 patients and included: abdominal pain (n=6), thrombosis (n=2), diarrhea (n=1) and pancreatitis (n=1). The median time from PEG-ASP administration to first toxic symptoms was 7 days (range 1-19), and there were also 4 (13%) early induction deaths. All deaths were observed in ≥50-year-old patients after a median of 5 days following PEG-ASP (range 1-9). Three of these four patients had massive obesity. While all expired patients had grade 4 neutropenia and thrombocytopenia at the time of death, sepsis was not present. Administration of PEG-ASP in induction remission for ALL patients resulted in a significant, but mostly reversible hepatotoxicity. This PEG-ASP treatment should be administered with caution for older, obese patients.