Longitudinal outcome over four decades of allogeneic stem cell transplantation: a single center experience.

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality.

Total body irradiation versus thiotepa/busulfan-based conditioning regimens for myeloablative allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia.

Total body irradiation (TBI)-based conditioning regimens are generally recommended for allogeneic HSCT (allo-HSCT) in patients with acute lymphoblastic leukemia (ALL). Recent evidence suggests that modern chemotherapy-based regimens may be as effective. This multicenter retrospective study compared the clinical outcomes of myeloablative allo-HSCT with thiotepa, busulfan, and cyclophosphamide/fludarabine (TTB) to TBI-based conditioning. Between 2002 to 2018, 63 and 114 patients received TTB- and TBI-based conditioning regimens, respectively. The 5-year cumulative incidence of relapse was lower in the TBI cohort compared to the TTB cohort (30% [95% CI, 22-38] versus 47% [95% CI, 36-59]; P = 0.03). Multivariate analysis identified T-ALL, Ph-negative B-ALL, and measurable residual disease associated with a higher relapse risk. The 5-year cumulative incidence of non-relapsed mortality (NRM) was significantly lower with TTB (12% [95% CI, 5-20]) compared to TBI (25% [95% CI, 18-33]) (P = 0.001). Multivariate analysis found TBI conditioning, older age, and advanced stages of ALL at transplantation associated with a higher NRM. No statistical difference was seen in overall survival (49% [95% CI, 40-58] and 46% [95% CI, 35-60]) in the TBI and TTB groups, respectively; P = 0.9). The study suggests that TTB-based conditioning may be a promising option for ALL patients undergoing allo-HSCT, as it resulted in similar OS and lower NRM than TBI-based conditioning.

Posttransplant cyclophosphamide versus anti-thymocyte globulin versus combination for graft-versus-host disease prevention in haploidentical transplantation for adult acute myeloid leukemia: A report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

BACKGROUND: The optimal choice for graft-versus-host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo-SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are two common strategies, but little is known about their combination. METHODS: Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo-SCT in complete remission between 2007 and 2021 at 260 EBMT-participating centers who received either PTCy (n = 2999), ATG (n = 358), or combination prophylaxis (n = 292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow-up was 31.8 months. RESULTS: On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female-to-male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p = .003), worse leukemia-free survival (HR, 1.4; p = .002), overall survival (HR, 1.49; p = .0009), and GVHD-free and relapse-free survival (HR, 1.29; p = .012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2-4 (HR, 0.51; p = .0003) and grade 3-4 (HR, 0.5; p = .018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. CONCLUSION: The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo-SCT for AML.

PTCy versus CNI-based GVHD prophylaxis in HLA-matched transplants for Hodgkin Lymphoma: a study of the LWP of the EBMT.

Studies comparing the efficacy of post-transplant cyclophosphamide (PTCy) to conventional calcineurin inhibitor (CNI)-based GVHD prophylaxis regimens in Hodgkin lymphoma (HL) patients are scarce. This study aimed to compare the outcomes of HL patients undergoing hematopoietic stem cell transplantation from HLA-matched donors who received GVHD prophylaxis with either PTCy or conventional CNI-based regimens, using data reported to the EBMT database between January 2015 and December 2022. Among the cohort, 270 recipients received conventional CNI-based prophylaxis and 176 received PTCy prophylaxis. Notably, PTCy prophylaxis was associated with delayed hematopoietic recovery, but also with a lower risk of chronic (25% versus 43%, p<0.001) and extensive chronic GVHD (13% versus 28% p=0.003) compared to the CNI-based cohort. The 2-year cumulative incidence of non-relapse mortality and relapse were 11% versus 17% (p=0.12), and 17% versus 30% (p=0.007) for PTCy and CNI-based, respectively. Moreover, the 2-year overall survival, progression-free survival and GVHD-free, relapse-free survival were all significantly better in the PTCy group compared with the CNI-based group: 85% versus 72% (p=0.005), 72% versus 53% (p<0.001), and 59% versus 31% (p<0.001), respectively. In multivariable analysis, PTCy was associated with a lower risk of chronic and extensive chronic GVHD, reduced relapse, and better OS, PFS, and GRFS compared to the CNI-based platform. Our findings suggest that PTCy as GVHD prophylaxis offers more favorable outcomes compared to conventional CNI-based prophylaxis in adult patients with HL undergoing HSCT from HLA-matched donors.

Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy.

BACKGROUND: This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. PATIENTS AND METHODS: The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). RESULTS: Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30 mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3-9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84-8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 109/L (OR 4.1, 95% C.I. 1.42-11.9, p = 0.009). In addition, the study found that ribavirin therapy significantly reduced progression to LRTD [OR 0.19, 95% C.I. 0.05-0.75, p = 0.018]. Co-infections (OR 5.7, 95% C.I. 1.4-23.5, p = 0.015) and ALC < 0.2 × 109/L (OR 17.7, 95% C.I. 3.6-87.1, p < 0.001) were independently associated with higher day + 100 after hPIV detection all-cause mortality. There were no significant differences in all-cause mortality and infectious mortality at day + 100 between the treated and untreated groups. CONCLUSION: ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.

Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT.

ABSTRACT: There is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete remission (CR1 or CR2). The primary end point was leukemia-free survival (LFS). Overall, 1011 patients were included with a median age of 54 years (range, 18-77). Donors had a median age of 29 years (range, 18-64); 304 (30%) were females, of which 150 (15% of the whole group) were donors to male recipients, and 621 (61%) were MUDs; 522 (52%) had negative cytomegalovirus (CMV-neg) serostatus, of which 189 (19%) were used for CMV-neg recipients. Donor age older than 30 years had a negative impact on relapse (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.06-1.8), LFS (HR, 1.4; 95% CI, 1.12-1.74), overall survival (HR 1.45; 95% CI, 1.14-1.85) and graft-versus-host disease (GVHD) free, relapse-free survival (HR, 1.29; 95% CI, 1.07-1.56). In addition, CMV-neg donors for CMV-neg recipients were associated with improved LFS (HR, 0.74; 95% CI, 0.55-0.99). The use of MMUD and female donors for male recipients did not significantly impact any transplant outcomes. For patients undergoing HSCT from a UD with PTCy for AML, donor age <30 years significantly improves survival. In this context, donor age might be prioritized over HLA match considerations. In addition, CMV-neg donors are preferable for CMV-neg recipients. However, further research is needed to validate and refine these recommendations.

Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies.

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3+ T cells, CD8+ T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4+ T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4+ T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning.

Haploidentical stem cell donor choice for patients with acute myeloid leukemia: a study from the ALWP of the EBMT.

ABSTRACT: There is a paucity of information to guide the selection of the most suitable donor in haploidentical (Haplo) hematopoietic stem cell transplantation (HSCT). For this reason, from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we conducted a retrospective analysis to evaluate the impact of Haplo donor characteristics on outcomes in patients with acute myeloid leukemia (AML) who received graft-versus-host disease prophylaxis with posttransplant cyclophosphamide (PTCy). The primary end point was graft-versus-host disease (GVHD)-free and relapse-free survival (GRFS). Overall, 2200 patients were included. The median age of donors was 37 years (range, 8-71); 820 (37%) were females, including 458 (21%) who were used for male recipients. In addition, 1631 donors (74%) donated peripheral blood (PB). Multivariable analysis identified certain donor-related risk factors with a detrimental impact on transplant outcomes. The use of PB, older donors' ages (>37 years), and female donors to male recipients negatively affected GRFS. Donor's age and female donor-to-male recipient combination also affected nonrelapse mortality, leukemia-free survival, and overall survival. In conclusion, donor-related variables significantly influence outcomes in patients with AML after Haplo-HSCT with PTCy. When possible, younger donors and male donors for male recipients should be prioritized. The use of bone marrow can additionally prevent GVHD.

Visual outcomes of combined use of implantable collamer lens implantation and laser corneal visual correction for myopia over -18.00 diopters.

PURPOSE: To explore visual outcomes in patients with extreme myopia receiving an implantable collamer lens (ICL) at -18.00 diopters (D), with central port, followed by bioptics by laser vision correction (laser in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]) to address residual myopia or myopic astigmatism. SETTING: Clínica Baviera (Aier Eye Hospital Group), Bilbao, Spain. DESIGN: Retrospective analysis of cases. METHODS: The study assessed uncorrected distance visual acuity, corrected distance visual acuity (CDVA), predictability, safety, efficacy, and patient satisfaction after implantation of the ICL and bioptics. The model implanted was V4c and EVO, with a correction of -18.00 D. Bioptics were performed at least 3 months after implantation, and patients were followed up for at least 3 months after LASIK or PRK. RESULTS: The analysis included 125 eyes from 90 patients. Of these, 51.2% underwent LASIK and 48.8% PRK. Mean time from implantation to bioptics was 5.9 ± 9.4 months. Patients were followed up for a mean of 40.2 ± 37.9 months after bioptics. Median manifest refractive spherical equivalent was -2.89 D before bioptics and -0.49 D after. Median CDVA was 0.18 logMAR before bioptics and 0.17 after. The mean safety and efficacy indices were 2.22 ± 1.88 and 2.06 ± 1.85, respectively. CONCLUSIONS: Visual outcomes and safety indices after ICL implantation and subsequent LASIK or PRK in patients with extreme myopia are excellent.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide.

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Ofatumumab as part of reduced intensity conditioning in high risk B-cell lymphoma patients: final long-term analysis from a prospective multicenter Phase-II Trial.

Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.

Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis in HLA-Matched and Haploidentical Donor Transplantation for Patients with Hodgkin Lymphoma: A Comparative Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising approach for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is a lack of studies examining the impact of this GVHD prophylaxis when different donor types are used in patients with Hodgkin lymphoma (HL). This study compared the outcomes of patients with HL undergoing HSCT from HLA-matched donors, including matched sibling donors (MSDs) and matched unrelated donors (MUDs), and haploidentical donors, using PTCy as the GVHD prophylaxis approach in all cohorts. We retrospectively compared outcomes of allo-HSCT from 166 HLA-matched donors (96 sibling and 70 unrelated donors) and 694 haploidentical donors using PTCy-based GVHD prophylaxis in patients with HL registered in the European Society for Blood and Marrow Transplantation database from 2010 to 2020. Compared to HLA-matched HSCT, haploidentical donor HSCT was associated with a significantly lower rate of platelet engraftment (86% versus 94%; P < .001) and a higher rate of grade II-IV acute GVHD (34% versus 24%; P = .01). The 2-year cumulative incidence of nonrelapse mortality (NRM) was significantly lower in the HLA-matched cohort compared to the haploidentical cohort (10% versus 18%; P = .02), resulting in a higher overall survival (OS) rate (82% versus 70%; P = .002). There were no significant differences between the 2 cohorts in terms of relapse, progression-free survival, or GVHD-free relapse-free survival. In multivariable analysis, haploidentical HSCT was associated with an increased risk of grade II-IV acute GVHD and NRM and worse OS compared to HLA-matched HSCT. Our findings suggest that in the context of PTCy-based GVHD prophylaxis, transplantation from HLA-matched donors appears to be a more favorable option compared to haploidentical HSCT.

Torque Teno Virus plasma DNA load: a novel prognostic biomarker in CAR-T therapy.

Torque Teno Virus (TTV) is a single-stranded circular DNA virus which has been identified as a surrogate marker of immune competence in transplantation. In this study we investigated the dynamics of plasma TTV DNAemia in 79 adult patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory large B-cell lymphoma, also evaluating the impact of TTV on immunotoxicities, response and survival outcomes. After lymphodepleting therapy, TTV DNA load was found to decrease slightly until reaching nadir around day 10, after which it increased steadily until reaching maximum load around day 90. TTV DNA load < 4.05 log10 copies/ml at immune effector cell-associated neurotoxicity syndrome (ICANS) onset identified patients at risk of progressing to severe forms of ICANS (OR 16.68, P = 0.048). Finally, patients who experienced falling or stable TTV DNA load between lymphodepletion and CAR-T infusion had better progression-free survival than those with ascending TTV DNA load (HR 0.31, P = 0.006). These findings suggest that TTV monitoring could serve as a surrogate marker of immune competence, enabling predictions of CAR-T efficacy and toxicity. This could pave the way for the development of TTV-guided therapeutic strategies that modulate clinical patient management based on plasma TTV load, similar to suggested strategies in solid organ transplant recipients.

Cord blood transplantation for AML: Comparable LFS in patients with de novo versus secondary AML in CR1, an ALWP/EBMT study.

We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T-cell depletion and no post-transplant cyclophosphamide. The primary end-point of the study was leukaemia-free survival (LFS). A total of 879 patients with de novo (n = 696) or secondary (n = 183) AML met the inclusion criteria. In multivariable analyses, sAML patients had non-significantly different LFS (HR = 0.98, p = 0.86), overall survival (HR = 1.07, p = 0.58), relapse incidence (HR = 0.74, p = 0.09) and non-relapse mortality (HR = 1.26, p = 0.13) than those with de novo AML. Our results demonstrate non-significantly different LFS following CBT in adult patients with secondary versus de novo AML.

Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy.

Epstein-Barr virus-positive (EBV+) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV+ PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV+ PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV+ PTLD following HCT to describe patients' demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV+ PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population.

Thiotepa-Based Regimens Are Valid Alternatives to Total Body Irradiation-Based Reduced-Intensity Conditioning Regimens in Patients with Acute Lymphoblastic Leukemia: A Retrospective Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Total body irradiation (TBI) at myeloablative doses is superior to chemotherapy-based regimens in young patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, in elderly and unfit patients, in whom reduced-intensity conditioning (RIC) regimens are preferred, whether a TBI-based or a chemotherapy-based approach is better is unexplored. Thiotepa can be used as part of ALL conditioning regimens. The current study aimed to compare transplantation outcomes after RIC with TBI-based or thiotepa-based regimens in patients with ALL. The study cohort comprised patients aged ≥40 years undergoing allo-HSCT for ALL in first complete remission between 2000 and 2020 who received an RIC regimen containing either TBI (4 to 6 Gy) or thiotepa. We identified a total of 265 patients, including 117 who received a TBI-based RIC regimen and 148 who received a thiotepa-based RIC regimen. Univariate analysis revealed no significant differences in the following transplantation outcomes for TBI versus thiotepa: relapse, 23% versus 28% (P = .24); nonrelapse mortality, 20% versus 26% (P = .61); leukemia-free survival, 57% versus 46% (P = .12); overall survival, 67% versus 56% (P = .18); graft-versus-host disease (GVHD]/relapse-free survival, 45% versus 38% (P = .21); grade II-IV acute GVHD, 30% in both groups (P = .84); grade III-IV acute GVHD, 9% versus 10% (P = .89). The sole exception was the incidence of chronic GVHD, which was higher in the recipients of TBI-based regimens (43% versus 29%; P = .03). However, multivariate analysis revealed no differences in transplantation outcomes between the 2 groups. In patients aged ≥40 years receiving RIC, use of a thiotepa-based regimen may represent a valid alternative to TBI-based regimens, as no differences were observed in the main transplantation outcomes.

Cord blood transplantation for adult mature lymphoid neoplasms in Europe and Japan.

ABSTRACT: To clarify the different characteristics and prognostic factors of cord blood transplantation (CBT) in adult patients with lymphoid neoplasms in Europe and Japan, we conducted a collaborative study. Patients aged 18-75 years receiving their first CBT (Europe: single CBT, n = 192; double CBT, n = 304; Japan: single CBT, n = 1150) in 2000-2017 were analyzed. Fewer patients with Hodgkin lymphoma (Europe vs Japan, 26% vs 5%), and older patients (≥50 years) (39% vs 59%) with a higher refined disease risk index (rDRI) (high-very high: 49% vs 14%) were included in the Japanese registry. High-very high rDRI was associated with inferior overall survival (OS) (vs low rDRI, Europe: hazard ratio [HR], 1.87; P = .001; Japan: HR, 2.34; P < .001) with higher progression/relapse risks. Total body irradiation (TBI)-containing conditioning contributed to superior OS both in Europe (vs TBI-reduced-intensity conditioning [RIC], non-TBI-RIC: HR, 1.93; P < .001; non-TBI-Myeloablative conditioning [MAC]: HR, 1.90; P = .003) and Japan (non-TBI-RIC: HR, 1.71; P < .001; non-TBI-MAC: HR 1.50, P = .007). The impact of HLA mismatches (≥2) on OS differed (Europe: HR, 1.52; P = .007; Japan: HR, 1.18; P = .107). CBT for lymphoid neoplasms, especially in those with high rDRI showed poor outcomes despite all the different characteristics in both registries. TBI should be considered in conditioning regimens to improve these outcomes. The different impacts of HLA mismatches call attention to the fundamental differences among these populations.

Comparison of Patients With Emmetropia and Presbyopia and Different Accommodation Who Undergo Unilateral or Bilateral Implantation of a Trifocal IOL.

PURPOSE: To compare visual outcomes and satisfaction in patients with emmetropia, presbyopia, and greater or lesser residual accommodation who undergo unilateral or bilateral implantation of a trifocal diffractive intraocular lens (IOL). METHODS: A multicenter, multisurgeon study was performed to evaluate outcomes in patients with emmetropia and presbyopia who underwent refractive lens exchange followed by implantation of a FineVision trifocal IOL (PhysIOL). The inclusion criteria were as follows: emmetropia, sphere -0.25 to +0.50 diopters (D), cylinder less than 0.75 D, and manifest refractive spherical equivalent (MRSE) of -0.25 to +0.25 D. All patients also had to have an uncorrected distance visual acuity (UDVA) of Snellen 0.9 or better in each eye. The sample was divided into different clusters based on two variables: eyes operated on (monocular or binocular) and age either younger than 55 years or 55 years or older. Thus, four possible groups were created. Visual and refractive performance, patient satisfaction, and spectacle independence were assessed. RESULTS: A total of 690 eyes from 431 patients were evaluated. There was no difference in postoperative uncorrected (UDVA) and corrected (CDVA) distance visual acuity between the groups. Binocular uncorrected near vision (UNVA) was better in patients who underwent surgery on both eyes regardless of age (median [interquartile range]: 0.00 [0.00; 0.10] vs 0.10 [0.00; 0.10] logMAR; P < .001). Binocular uncorrected intermediate vision (UIVA) was better in patients who underwent surgery on both eyes aged younger than 55 years than in those who underwent surgery in one eye aged 55 years or older (median [interquartile range]: 0.18 [0.10; 0.18] vs 0.30 [0.18; 0.30] logMAR; P < .001). The efficacy and safety indexes were 0.98 ± 0.09 and 1.01 ± 0.06, respectively. A total of 93.3% of eyes were within the 0.50 D range in postoperative MRSE. Visual dysphotopsia was worse in patients with both eyes operated on, although the differences were not statistically significant. CONCLUSIONS: The study shows that after refractive lens exchange, patients with emmetropia and presbyopia who received a trifocal IOL in one or both eyes achieved good UNVA, UIVA, and UDVA. Regarding near binocular visual acuity, results were better for patients who underwent surgery on both eyes than for those who underwent surgery on one eye. Regarding binocular intermediate visual acuity, patients aged younger than 55 years with both lenses replaced had better results than those 55 years or older with only one lens replaced. However, no significant differences were observed in UDVA or patient satisfaction. [J Refract Surg. 2023;39(12):817-824.].

Recent advances in allogeneic transplantation for acute myeloid leukemia.

PURPOSE OF REVIEW: This review highlights recent advancements in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute myeloid leukemia (AML). RECENT FINDINGS: Important improvements have been observed throughout the allo-HSCT procedure and patient management. Universal donor availability and reduced risk of graft-versus-host disease (GVHD) have been achieved with the introduction of posttransplant cyclophosphamide for GVHD prophylaxis. It has contributed, together with advances in conditioning regimens, GVHD treatment and supportive care, to a reduced overall toxicity of the procedure. Relapse is now the most frequent cause of transplant failure. With increased knowledge of the biological characterization of AML, better prediction of transplant risks and more profound and standardized minimal residual disease (MRD) monitoring, pharmacological, and immunological strategies to prevent relapse are been developed. SUMMARY: Allo-HSCT remains the standard of care for high-risk AML. Increased access to transplant, reduced toxicity and relapse are improving patient outcomes. Further research is needed to optimize MRD monitoring, refine conditioning regimens, and explore new GVHD management and relapse prevention therapies.

Impact of SCHOLAR-1 Criteria on Chimeric Antigen Receptor T Cell Therapy Efficacy in Aggressive B Lymphoma: A Real-World GELTAMO/GETH Study.

In the pre-chimeric antigen receptor T cell (CAR-T) therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real-world data from Spain, focused on this SCHOLAR-1 refractory group, and compared patients who underwent CAR-T therapy with the previous standard of care. In this study, we found that the efficacy of CAR-T therapy in refractory patients, in terms of progression-free survival (PFS) and overall survival (OS), was superior to that of the treatments available in the pre-CAR-T era. The main objective of these new analyses was to analyze treatment efficacy in terms of response rates and survival for patients with ABCL with or without the SCHOLAR-1 criteria. In addition, we analyzed the prognostic impact of each SCHOLAR-1 criterion independently. Our study aimed to assess the prognostic impact of SCHOLAR-1 criteria on ABCL patients treated with CAR-T therapy in Spain. This multicenter, retrospective, observational study. We included all adult patients treated with commercially available CAR-T cell products and diagnosed with ABCL different from primary mediastinal large B cell lymphoma between February 2019 and July 2022. Patients meeting any SCHOLAR-1 criteria (progressive disease as the best response to any line of therapy, stable disease as the best response to ≥4 cycles of first-line therapy or ≥2 cycles of later-line therapy, or relapse at <12 months after autologous stem cell transplantation [auto-SCT]) in the line of treatment before CAR-T therapy (SCHOLAR-1 group) were compared with those not meeting any of these criteria (non-SCHOLAR-1 group). To analyze the prognostic impact of individual SCHOLAR-1 criteria, all the patients who met any of the SCHOLAR-1 criteria at any time were included to assess whether these criteria have the same prognostic impact in the CAR-T era. In addition, patients were grouped according to whether they were refractory to the first line of treatment, refractory to the last line of treatment, or relapsed early after auto-SCT. The PFS and OS were calculated from the time of appearance of the SCHOLAR-1 refractoriness criteria. Of 329 patients treated with CAR-T (169 with axi-cel and 160 with tisa-cel), 52 were in the non-SCHOLAR-1 group and 277 were in the SCHOLAR-1 group. We found significantly better outcomes in the non-SCHOLAR-1 patients compared with the SCHOLAR-1 patients (median PFS of 12.2 and 3.3 months, respectively; P = .009). In addition, axi-cel showed better results in terms of efficacy than tisa-cel for both the non-SCHOLAR-1 group (hazard ratio [HR] for PFS, 2.7 [95% confidence interval (CI), 1.1 to 6.7; P = .028]; HR for OS, 7.1 [95% CI, 1.5 to 34.6; P = .015]) and SCHOLAR-1 group (HR for PFS, 1.8 [95% CI, 1.3 to 2.5; P < .001]; HR for OS, 1.8 [95% CI, 1.2 to 2.6; P = .002]), but also significantly more toxicity. Finally, separately analyzing the prognostic impact of each SCHOLAR-1 criterion revealed that refractoriness to the last line of treatment was the variable with the most significant impact on survival. In conclusion, SCHOLAR-1 refractoriness criteria notably influence the efficacy of CAR-T therapy. In our experience, axi-cel showed better efficacy than tisa-cel for both SCHOLAR-1 and non-SCHOLAR-1 patients. Refractoriness to the last line of treatment was the variable with the most significant impact on survival in the CAR-T therapy era.