Haploidentical hematopoietic cell transplantation using in vitro T cell depleted grafts as salvage therapy in patients with disease relapse after prior allogeneic transplantation

Abstract

Disease relapse after one or more allogeneic hematopoietic cell transplantations (HCT) represents a therapeutic challenge with all options bearing a significant morbidity and mortality. Haploidentical HCT may induce more pronounced anti-leukemic effects and was evaluated at our center in 25 consecutive patients with disease relapse after preceding HCT receiving haploidentical grafts after in vitro T cell depletion. Overall survival at 1 and 2 years was 32 and 14%, respectively. Of note, patients with complete remission (CR) before haploidentical HCT had a very favorable overall survival of 41.7% at 2 years. Cumulative incidence of non-relapse mortality was 36 and 40% at 1 and 2 years, respectively. With a cumulative incidence for relapse of 36 and 45.6% at 1 and 2 years, disease-free survival (DFS) was 28 and 14.4%, respectively. Here also, patients with CR before haploidentical HCT had a favorable DFS of 42% at 2 years. Only very limited acute (11 patients (44%) with a median grade 1) and chronic graft versus host disease (GvHD) (5 patients (11%), limited grade only) was observed. The main complications and causes of death comprised-besides relapse-infections and bleeding complications. Hence, haploidentical HCT can achieve long-term survival comparable to second transplantation with matched or mismatched donors for patients with otherwise deleterious prognosis and should be considered as a treatment option for patients experiencing disease relapse after previous allogeneic HCT.

Haploidentical transplants for patients with relapse after the first allograft

“…5,7,15,16 Switching donors has been advocated; however, studies to date are inconsistent, and several groups have reported limited benefit. [16][17][18][19] Despite that, our group has traditionally changed conditioning (patients who received busulfan-based conditioning for the first transplant received melphalan-based conditioning for the second one, and vice versa) and changed donor, including for patients who had a haploiodentical donor for the first transplant.…”

New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

“…Further, salvage allogeneic hematopoietic stem cell transplantation (HSCT) has shown limited efficacy with a high relapse rate in this population (3,4). Therefore, the development of novel strategies to induce CR and extend the survival of such patients is essential.…”

“…Although the outcome of newly diagnosed acute lymphoblastic leukemia (ALL) has been substantially improved by intensive chemotherapy regimens and novel targeted drugs, patients progressing to the relapsed or refractory (r/r) stage exhibit poor prognosis ( 1 ), with a complete remission (CR) rate of 30–45% and a median overall survival (OS) of 5–9 months ( 2 ). Further, salvage allogeneic hematopoietic stem cell transplantation (HSCT) has shown limited efficacy with a high relapse rate in this population ( 3 , 4 ). Therefore, the development of novel strategies to induce CR and extend the survival of such patients is essential.…”

Donor‐derivedCD19‐targeted T cell infusion induces minimal residual disease‐negative remission in relapsed B‐cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation

“…Few studies have investigated the effectiveness of a second course of haplo‐HSCT for the treatment of relapsed ALL after haplo‐HSCT. In a study of 25 consecutive patients who relapsed after initial HSCT, Haen et al () found that treatment with haploidentical grafts after in vitro T‐cell depletion resulted in 1‐ and 2‐year overall survival rates of 32% and 14%, respectively. In a previous study, we found that the overall survival rate and non‐relapse mortality rate after a second allogeneic HSCT (allo‐HSCT) were approximately 30·9% and 35·1%, respectively, among patients with relapsed haematological malignancies (some patients received DLI before the second allo‐HSCT) (Chen et al , ).…”