The use of MSCs in steroid-refractory acute GvHD in Europe: a survey from the EBMT cellular therapy & immunobiology working party
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Myeloablative conditioning in cord blood transplantation for acute myeloid leukemia patients is efficacious only until age 55
Umbilical cord blood transplantation (CBT) is accepted as an effective treatment for acute myeloid leukemia (AML), and reduced-intensity conditioning (RIC), rather than myeloablative conditioning (MAC) regimens allowed elderly patients to be treated safely. However, appropriate intensities of conditioning regimens are still unclear, especially for middle-aged patients. To compare outcomes after RIC and MAC regimens, we analyzed AML patients aged 16 years or older in the Japanese registry database, who underwent single cord unit CBT between 2010-2019. Median ages of the RIC group (n = 1353) and the MAC group (n = 2101) were 59 and 51 years (P < 0.001), respectively. 5-year overall survival (OS) after MAC was superior to that of RIC (38.3% vs 27.7%, P < 0.001) with lower incidence of relapse (33.9% vs 37.4%, P = 0.029) and better neutrophil engraftment (84.7% vs 75.9%, P < 0.001). Detailed subgroup analysis revealed that age at transplantation is the most important factor affecting 5-year OS in RIC and MAC. This analysis identified a threshold of 55 years, beyond which the superiority of MAC disappeared, irrespective of other factors such as disease status or performance status. In conclusion, RIC may be preferable for patients aged 56 or older in CBT for AML due to higher potential toxicities.
Melphalan-based conditioning with post-transplant cyclophosphamide for peripheral blood stem cell transplantation: donor effect
Fludarabine and melphalan (FM) conditioning offers effective disease control with an acceptable toxicity profile. Post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has improved transplant outcomes. We retrospectively reviewed patients receiving FM-based transplants with PTCy at City of Hope. Of 248 patients included, 89 (35.9%) received hematopoietic cell transplant (HCT) from a matched related/unrelated donor (MRD/MUD), 118 (47.6%) from a haploidentical (HID) donor, and 49 (19.8%) from a mismatched unrelated donor (MMUD). There were no differences in acute and chronic GVHD based on donor type. The 2-year overall survival (OS) for patients receiving HID, MMUD, and MRD/MUD was 58%, 55%, and 70%; disease-free survival (DFS) was 52%, 48%, and 66%; and graft-versus-host/relapse-free survival (GRFS) were 48%, 40%, and 59%, respectively. OS, DFS, and GRFS were similar regardless of donor type on multivariable analysis. However, donor age ≥35 years was associated with lower OS and GRFS and higher 2-year non-relapse mortality (NRM) on multivariable analysis across all patients, regardless of donor type. FM with PTCy appears to produce similar outcomes between MRD/MUD, MMUD, and HID when adjusting for donors <35 years, and donor age seems to be the most important factor when selecting a donor with this regimen.
The 2023 EBMT report on hematopoietic cell transplantation and cellular therapies. Increased use of allogeneic HCT for myeloid malignancies and of CAR-T at the expense of autologous HCT
In 2023, 47,731 HCT (20,485 (42.9%) allogeneic and 27,246 (57.1%) autologous) in 43,902 patients were reported by 696 European centers. 6042 patients received advanced cellular therapies, 4888 of which were CAR-T. Compared to the previous year there was an increase in CAR-T (+52.5%), in allogeneic HCT (+7.8%) but none in autologous HCT (+0.4%). Main indications for allogeneic HCT were myeloid (11,748; 60.7%), lymphoid malignancies (4,850; 25.0%), and non-malignant disorders (2558; 13.2%). Use of allogeneic HCT increased for AML (+12.1%) and for NHL (+11.0%), particularly in T-NHL (+25.6%). Main indications for autologous HCT were lymphomas (7890; 32.2%), PCD (14,271; 58.2%), and solid tumors (1608; 6.6%) with recovering numbers for autoimmune diseases. In patients with allogeneic HCT, the use of sibling donors increased by +1.0%, haploidentical donors by +11.7%, and unrelated donors by +11.1%. Cord blood HCT decreased again by −5.4%. Pediatric HCT activity increased slightly (5455; +0.1%) with differences between allogeneic (4111; −0.5%) and autologous HCT (1344: +1.7%). Use of CAR-T increased to a cumulative total of 13,927 patients including patients treated for autoimmune diseases. Overall, numbers show a complete recovery from the pandemic dip with increased cellular therapy at the expense of autologous HCT. Allogeneic HCT activity focuses on myeloid malignancies.
Close relationship partners of impartial altruists do not report diminished relationship quality and are similarly altruistic
Impartial altruism is often considered a moral ideal but is rare in practice. Instead, generosity typically decreases as social distance increases, a phenomenon termed social discounting. Most people prefer this partiality in their close relationships and view impartial altruists as poorer relationship partners. This suggests real-world impartial altruism may be rare because it reduces—or is perceived to reduce—the quality of close relationships. To investigate this, we compared patterns of generosity and social relationship quality in a rare sample of individuals who had engaged in extraordinary real-world impartial altruism (altruistic kidney donors; n = 59) and their closest friend or family member (n = 59) to controls (n = 71) and their closest others (n = 71). We designed a direct test of third-party social discounting, which experimentally confirmed real-world altruists’ impartiality, finding that they are more likely than controls to split resources evenly between close and distant others rather than favoring close others. However, we found no statistically significant association between impartial altruism and social relationship quality. Instead, we found that altruists’ close others also show more impartiality than controls. This suggests value homophily (shared moral values) among altruists, which may represent a protective factor for close relationships in the context of impartial altruism.
Intermediate-dose TBI/fludarabine conditioning for allogeneic hematopoietic cell transplantation in patients with peripheral T-cell lymphoma
Allogeneic hematopoietic cell transplantation (alloHCT) is an effective treatment for patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), but the contribution of the conditioning regimen is still unclear. Here we present a retrospective single-center study using conditioning with intermediate-dose total body irradiation (TBI) and fludarabine for alloHCT in PTCL. Forty-seven patients underwent alloHCT for PTCL between 2010 and 2023 after conditioning with fludarabine and intermediate-dose TBI (8 Gy in 87% of the cases). In most patients alloHCT was administered as part of second-line therapy, in 22 (47%) patients after having been primary refractory, and 21 (45%) of the patients were chemoresistant at alloHCT. With a median follow-up of 5.5 years, 5-year progression-free survival (PFS), overall survival, relapse incidence, and non-relapse mortality were 61%, 65%, 24%, and 15%, respectively. The 5-year PFS of patients transplanted with stable disease and progressive disease was 57% and 26%, respectively. Of 11 relapses, only 2 (18%) occurred beyond 6 months post transplant, and no relapse was observed after onset of chronic graft-versus-host disease. AlloHCT with intermediate-dose TBI/fludarabine conditioning is associated with a favorable toxicity/efficacy profile and can provide durable survival in a substantial fraction of patients with PTCL including those with poorly controlled disease at transplant.
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