1.
Donor Lymphocyte Infusion and Molecular Monitoring for Relapsed Myelofibrosis After Hematopoietic Cell Transplantation
Gagelmann, N., Wolschke, C., Badbaran, A., Janson, D., Berger, C., Klyuchnikov, E., Ayuk, F., Fehse, B., Kröger, N.
HemaSphere. 2023;7(7):e921
Abstract
Hematopoietic cell transplantation (HCT) is a curative approach for myelofibrosis patients, but relapse is a major cause of treatment failure. We investigated the effect of donor lymphocyte infusion (DLI) in 37 patients with molecular (n = 17) or hematological relapse (n = 20) after HCT. Patients received median of 2 (range, 1-5) cumulative DLI (total of 91 infusions). Median starting dose was 1 × 10(6) cells/kg, escalated by half-log ≥6 weeks if no response nor graft-versus-host disease (GvHD) occurred. Median time to first DLI was 40 weeks for molecular relapse versus 145 weeks for hematological relapse. Overall molecular complete response (mCR) at any time was 73% (n = 27) and was significantly higher for initial molecular relapse (88%) versus hematological relapse (60%; P = 0.05). The 6-year overall survival was 77% versus 32% (P = 0.03). Acute GvHD 2-4 occurred in 22% and half of the patients achieved mCR without any GvHD. All patients who relapsed from mCR achieved after first DLI could be salvaged with subsequent DLI, showing long-term survival. No second HCT was needed for molecular relapse versus 6 for hematological relapse. This comprehensive and largest study to date suggests molecular monitoring together with DLI as standard of care and a crucial approach to achieve excellent outcomes in relapsed myelofibrosis.
2.
Differential effects of donor lymphocyte infusion upon treatment response and GVHD according to relapse level and donor sources in patients with myelodysplastic syndrome
Park, S., Kim, T. Y., Lee, J. H., Lee, J. Y., Min, G. J., Park, S. S., Yahng, S. A., Shin, S. H., Yoon, J. H., Lee, S. E., et al
Therapeutic advances in hematology. 2021;12:20406207211043748
Abstract
INTRODUCTION Donor lymphocyte infusion (DLI) is one of the effective options for post-transplant disease control of myelodysplastic syndrome (MDS). Its success or failure depends on the induction of antitumor immune reactions, durability of clinical responses, and severity of unwanted toxicities mainly from graft-versus-host disease (GVHD). METHODS By analyzing 61 patients receiving DLI for post-transplant MDS relapse, we assessed treatment outcomes and affecting factors, especially focusing on the level of relapse (hematological, molecular, and imminent relapse). RESULTS The response rate (42.1%, 36.4%, 72.7%), and overall survival (OS) at 2?years (27.8%, 45.5%, 70.1%) were different for each relapse level with imminent relapse group showing the most promising results. For OS, response to DLI or pre-DLI chemotherapy, and time to relapse were independent prognostic factors. Meanwhile, post-DLI GVHD and time to relapse were independently predictive for DLI response; post-DLI GVHD was predictive for DLI response, but not for OS, suggesting a potential detrimental impact of GVHD on survival. The incidence of GVHD and GVHD-related deaths were 37.7% and 10.0%, respectively, and CD3(+) cell doses triggering GVHD tended to be lower in cases with haploidentical donor or imminent relapse. CONCLUSION Despite being limited by small number of cases and its retrospective nature, this study again demonstrated the therapeutic effects of DLI in relapsed MDS, and that earlier detection and intervention at lower level relapse might possibly be associated with better results. Furthermore, we propose that tailored cell dosing schedule based on relapse level and donor source may be helpful in minimizing fatal GVHD.
3.
Comparison of second transplantation and donor lymphocyte infusion for donor mixed chimerism after allogeneic stem cell transplantation for nonmalignant diseases
Umeda, K., Adachi, S., Tanaka, S., Miki, M., Okada, K., Hashii, Y., Inoue, M., Cho, Y., Koh, K., Goto, H., et al
Pediatric Blood & Cancer. 2016;63(12):2221-2229
Abstract
BACKGROUND Donor mixed chimerism (MC) is an increasing problem after hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases. PROCEDURE In this study, a self-administered questionnaire was used to retrospectively compare efficacy and safety in 49 patients undergoing second HSCT (n = 13) or donor lymphocyte infusion (DLI; n = 36) as treatment for MC. RESULTS The response rate to DLI of patients with secondary graft failure (GF) (25.0%) was significantly lower than that of patients without secondary GF (81.3%; P = 0.041). Among patients undergoing DLI, the rates of successful response were significantly higher in patients having at least 30% donor chimerism (94.1%) than in patients having less than 30% donor chimerism (61.1%; P = 0.041). Furthermore, the rates of successful response were significantly higher in patients receiving larger first or maximum doses of DLI. Sixteen (50.0%) of 32 patients without secondary GF attained complete chimerism after DLI. The cumulative incidence of grade II-IV acute graft-versus-host disease and cytopenia was 37.6 and 26.1%, respectively. CONCLUSIONS DLI yields promising response rates in most patients with higher donor chimerism levels, whereas second HSCT is more likely to benefit patients with lower donor chimerism levels. Copyright © 2016 Wiley Periodicals, Inc.