Abstract Background: Autologous stem cell transplantation (ASCT) is the standard treatment for peripheral T-cell lymphomas (PTCLs). Strategies that reduce the relapse rate and treatment-related mortality are essential for successful ASCT. Because in vivo/in vitro purging methods using rituximab are not appropriate for T-cell lymphomas, an ex vivo CD34+ selective purging system is the most reliable method to reduce autograft tumor cell contamination in these tumors. Methods: We retrospectively investigated the influence of ex vivo purging with CD34+ selection to maximize the effects of ASCT. Of 67 consecutive PTCL patients, 32 and 35 underwent purged and unpurged ASCT. Results: The purged group had improved overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (hazard ratio [HR] = 2.68, p = 0.016; HR = 3.97, p = 0.002; and HR = 3.65, p = 0.004, respectively), compared to the unpurged group. Prognostic factor analysis showed that unpurged ASCT, chromosomal abnormalities at initial diagnosis, high risk, and pre-ASCT disease status were associated with poor survival outcomes. Subgroup analysis demonstrated that purging was most appropriate for International Prognostic Index high-risk patients who underwent upfront ASCT (HR = 3.35 [OS] and = 6.59 [DFS]). In purged ASCT group, NK cell activity and the lymphocyte-to-monocyte ratio known as an independent prognostic factor were increased after ASCT with statistical significance. Conclusions: There were no engraftment failures or differences in adverse events between the two groups. CD34+ ex vivo purging ASCT is safe, effective, and may improve survival outcomes, particularly in high-risk PTCL patients.
Inotuzumab ozogamicin (INO) showed improved treatment outcomes for relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) but can induce hepatotoxic adverse events. Hepatic venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) frequently develops after allogeneic hematopoietic cell transplantation (allo-HCT), and INO is a strong pretransplant risk factor. However, VOD/SOS can occur just after INO therapy. Here, we describe a BCP-ALL patient treated with INO for isolated extramedullary relapse after allo-HCT. The patient experienced elevated liver enzymes with ascites at 21 days from the last INO dose. Although she met the criteria for VOD/SOS, the diagnosis was challenging because of her ongoing hepatic graft- versus-host disease (GVHD) and normal portal vein flow on Doppler sonogram. The radiologist suggested liver cirrhosis based on computed tomography, with VOD/SOS, liver cirrhosis, and GVHD assumed to be differential diagnoses. She received supportive care with GVHD management; however, due to progressive hepatic failure, we conducted emergent deceased-donor liver transplantation, and the pathologic findings indicated VOD/SOS. Her leukemia was stable, but she died of sepsis after 3 months. INO use is a high-risk factor for VOD/SOS, but an accurate diagnosis can be challenging due to various hepatic complications. Early diagnosis and proper management for VOD/SOS is important for improved outcomes.
Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.
Intensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking.Therefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined.All GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival.This study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.
Abstract Objective We investigated the role of anti‐thymocyte globulin (ATG; Thymoglobulin) in matched sibling donor hematopoietic stem cell transplantation (MSD‐HSCT) after reduced intensity conditioning (RIC) in myelodysplastic syndrome (MDS). Methods Forty‐seven patients with 10 mg/kg ATG (ATG group; median age 53 years) and 33 without ATG (no‐ATG group; median age 43, P < .0001) were compared. Results Median time to engraftment was similar. Two‐year cumulative incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) was significantly lower in the ATG group (15% vs 55%, P < .0001), while that of acute GVHD was similar compared with the no‐ATG group. After a median follow‐up of 60 months (range, 14‐184), the 3‐year cumulative incidences of non‐relapse mortality and relapse were 9% and 21% for ATG group and 15% and 19% for no‐ATG group ( P = .408 and P = .717), respectively, leading to a significantly better 3‐year GVHD‐free and relapse‐free survival (GRFS) in the ATG group (55% vs 19%, P = .006): The 3‐year overall and disease‐free survival were similar. Infectious complication occurred with similar frequencies in both groups. Conclusion These findings suggest that ATG can be safely used to decrease moderate‐to‐severe chronic GVHD with improved GRFS for patients with MDS receiving MSD‐HSCT in RIC setting.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)