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The article presents brief information on the benefits of the trees of Forest Park situated in Saint Louis, Missouri. It states that he trees of Forest Park has been the focus of a major restoration effort, and which mainly consist of broad leaf deciduous trees. A pie chart depicting annual distribution of the benefits of Forest Park's Trees, and a graph depicting number of trees in Forest Park's developed areas, by zone, are also offered.

JC virus-specifi c CD8+ cytotoxic T lymphocytes are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy. However, very few JC virus T cell epitopes restricted to MHC class I have been defined. Of the two HLA-A*0201-restricted JCV epitopes, VP1p36 and VP1p100, studies have shown that they are conserved T cell epitopes of polyomaviruses. The cross-recognition associated to these epitopes has complicated the efforts of understanding the dynamics of immune response to JC virus. Based on the previously identified HLA-A*0201 binding T cell epitope of Simian virus 40 T antigen P281-289 (KCDDVLLLL) and BK virus T antigen P558-566 (SLQNSEFLL), T cell epitopes of JC Virus T antigen P282-290 (KCEDVFLLM) and P557-565 (SLSCSEYLL) were identified. In this report, we demonstrated that JC Virus P282-290 and P557-565 were able to stimulate T cell responses in healthy donors' PBMCs and CD8+ cytotoxic T lymphocytes raised with both peptides could recognize and lyse their targets. Most importantly, there were no T cell cross-recognitions between JC Virus, BK Virus and SV40 virus. Therefore, JCV T-ag epitopes P282-290 and P557-565 could be better antigen epitopes compared to VP1p36 and VP1p100 to study the dynamics of cellular immune response to JCV in PML patients. In addition, as a HLA-A*0201 binding T cell epitope, both peptides could be a valuable component of immunotherapies aiming at increasing the cellular immune response against JCV for the treatment of progressive multifocal leukoencephalopathy. [ABSTRACT FROM AUTHOR]

Nephropathy associated with BK virus has emerged as an important cause of allograft failure in renal transplant recipients. Here we exploited a recently developed novel monocyte based solid phase T cell selection system, in which monocytes are immobilized on solid support, for antigen-specific T cell purification. The underlying hypothesis of this new method is that antigen-specific T cells recognize, bind their cognate antigens faster than non-specific T cells and are concentrated on the surface after removing the non-adherent cells by washing. Moreover, activated antigen-specific T cells proliferate more rapidly than non-specific T cells, further increasing the frequency and purity of antigen-specific T cells. Optimal selection times for BK virus-specific T cells are studied. Our data demonstrated that T cell selection can usually increase the frequency of antigen-specific T cells by >10 fold, whereas T cell expansion following the selection boost the frequency of antigen-specific T cells by another ~10 fold. This new T cell selection system is superior to traditional stimulation method (i.e. simply mixing antigen presenting cells and lymphocytes together) in generating antigen-specific T cells. This inexpensive and simple T cell selection system can produce large quantity of highly purified BK virus-specific T cells within 1-2 weeks after initial T cell activation. [ABSTRACT FROM AUTHOR]

We have fabricated PrBa[sub 2][Cu[sub 1-x]Ga[sub x]][sub 3]O[sub 7] (PBGCO) ceramic samples for x = 0.05, 0.10, 0.15 and 0.20. The electrical resistivities of these samples are many orders of magnitude higher than that of PrBa[sub 2]Cu[sub 3]O[sub 7] (Pr123) while the other physical properties remain much the same. PBGCO therefore may be a possible buffer layer for YBa[sub 2]Cu[sub 3]O[sub 7-δ] (Y123) superlattices/multilayers. For this reason YBa[sub 2]Cu[sub 3]O[sub 7-δ]/PrBa[sub 2](Cu[sub 0.8]Ga[sub 0.2])[sub 3]O[sub 7] (Y123/PBCGO) and YBa[sub 2]Cu[sub 3]O[sub 7-δ]/Y[sub 0.4]Pr[sub 0.6]Ba[sub 2]Cu[sub 3]O[sub 7] (Y123/YPBCO) superlattices were fabricated and their transport properties were studied. It is found that although PBGCO is better for insulating Y123 films in trilayers, inter-Y123 layer coupling exists between separated Y123 layer&deg. [ABSTRACT FROM AUTHOR]

• There was high tolerance of radiation-based myeloablative conditioning with cyclophosphamide. • With the use of 3 GVHD prophylaxis agents, relapse was a major barrier to survival. • Doses of T cells not exposed to cyclophosphamide were associated with less relapse. The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization. After conditioning, patients received their grafts in 2 components: (1) a fixed dose of 2 × 108/kg T cells, followed 2 days later by CY, and (2) a CD34-selected graft containing a small residual amount of non-CY-exposed T cells, at a median dose of 2.98 × 103/kg. Forty-six patients with hematologic malignancies were treated. Despite the myeloablative conditioning regimen and use of high T cell doses, the cumulative incidences of grade II-IV acute GVHD, chronic GVHD, and NRM at 1 year and 5 years were very low, at 13%, 9%, and 4.3%, respectively. This contributed to a high overall survival of 89.1% at 1 year and 65.8% at 5 years. Relapse was the primary cause of mortality, with a cumulative incidence of 23.9% at 1 year and 45.7% at 5 years. In a post hoc analysis, relapse rates were significantly lower in patients receiving greater than versus those receiving less than the group median of non-CY-exposed residual T cells in the CD34 product (19.3% versus 58.1%; P =.009), without a concomitant increase in NRM. In its current form, this 2-step regimen was highly tolerable, but strategies to reduce relapse, potentially the addition of T cells not exposed to CY, are needed. [ABSTRACT FROM AUTHOR]

Haploidentical stem cell transplantation (SCT) offers a transplantation option to patients who lack an HLA-matched donor. We developed a 2-step approach to myeloablative allogeneic hematopoietic stem cell transplantation for patients with haploidentical or matched related (MR) donors. In this approach, the lymphoid and myeloid portions of the graft are administered in 2 separate steps to allow fixed T cell dosing. Cyclophosphamide is used for T cell tolerization. Given a uniform conditioning regimen, graft T cell dose, and graft-versus-host disease (GVHD) prophylaxis strategy, we compared immune reconstitution and clinical outcomes in patients undergoing 2-step haploidentical versus 2-step MR SCT. We retrospectively compared data on patients undergoing a 2-step haploidentical (n = 50) or MR (n = 27) peripheral blood SCT for high-risk hematological malignancies and aplastic anemia. Both groups received myeloablative total body irradiation conditioning. Immune reconstitution data included flow cytometric assessment of T cell subsets at day 28 and 90 after SCT. Both groups showed comparable early immune recovery in all assessed T cell subsets except for the median CD3/CD8 cell count, which was higher in the MR group at day 28 compared with that in the haploidentical group. The 3-year probability of overall survival was 70% in the haploidentical group and 71% in the MR group ( P = .81), while the 3-year progression-free survival was 68% in the haploidentical group and 70% in the MR group ( P = .97). The 3-year cumulative incidence of nonrelapse mortality was 10% in the haploidentical group and 4% in the MR group ( P = .34). The 3-year cumulative incidence of relapse was 21% in the haploidentical group and 27% in the MR group ( P = .93). The 100-day cumulative incidence of overall grades II to IV acute GVHD was higher in the haploidentical group compared with that in the MR group (40% versus 8%, P < .001), whereas the grades III and IV acute GVHD was not statistically different between both groups (haploidentical, 6%; MR, 4%; P = .49). The cumulative incidence of cytomegalovirus reactivation was also higher in the haploidentical group compared to the MR group (haploidentical, 68%; MR, 19%; P < .001). There were no deaths from GVHD in either group. Using an identical conditioning regimen, graft T cell dose, and GVHD prophylaxis strategy, comparable early immune recovery and clinical outcomes were observed in the 2-step haploidentical and MR SCT recipients. [ABSTRACT FROM AUTHOR]

Haploidentical hematopoietic stem cell transplantation (HSCT) is an attractive alternative donor option based on the rapid availability of an acceptable donor for most patients and decreased cost compared with costs of other alternative donor strategies. The safety of haploidentical HSCT has increased in recent years, making it ethically feasible to offer to patients with earlier stage disease. We developed a 2-step approach to haploidentical HSCT that separates the lymphoid and myeloid portions of the graft, allowing fixed T cell dosing to improve consistency in outcome comparisons. In the initial 2-step trial, the subset of patients without morphologic disease at HSCT had high rates of disease-free survival. To confirm these results, 28 additional patients without evidence of their disease were treated and are now 15 to 45 (median, 31) months past HSCT. To date, the 2-year cumulative incidence of nonrelapse mortality is 3.6%, with only 1 patient dying of nonrelapse causes, confirming the safety of this approach. Based on low regimen toxicity, the probabilities of disease-free and overall survival at 2 years are 74% and 77%, respectively, consistent with the findings in the initial trial and supporting the use of this approach in earlier stage patients lacking a matched related donor. [ABSTRACT FROM AUTHOR]

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 108/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplant (HSCT) remains the only potentially curative treatment for many hematologic malignancies (HM). We previously developed a two-step approach that separates the lymphoid and myeloid portions of the graft, allowing a consistent T cell dosing and sparing the stem cells from the effect of post-transplant cyclophosphamide (CY). The two-step approach demonstrated safety and efficacy in patients treated with myeloablative and reduced-intensity conditioning. Here, we extended our two-step platform to older and less fit patients and explored the effects of using a high dose of T cells on disease relapse and transplant outcomes. Thirty-four patients with HM were treated. Median age was 68 years old and included a minority population constituting 32%. Eighty-two percent had a hematopoietic cell transplantation comorbidity index score ≥3. Ninety-one percent were haploidentical, and the rest were matched-related donor HSCT. Following administration of fludarabine and 2 Gy total body irradiation (TBI) (13 patients) or 4 Gy TBI (21 patients) conditioning regimen, a fixed dose of 2 × 10 8 /kg CD3+ T cells was given, followed 2 days later by CY, then infusion of CD34-selected stem cells. Overall survival (OS) was 70% at 1 year and 48% at 3 years. The cumulative incidence (CI) of non-relapse mortality (NRM) and relapse were 22% and 33% at 3 years. However, the CI of relapse was much lower for patients treated with 4 Gy TBI versus those treated with 2 Gy TBI (11% versus 54%, P = .045), while NRM was similar (23% versus 15%, P = .399). This contributed to a high OS of 64% in patients who received 4 Gy TBI-based conditioning at 3 years, with median OS not reached, although this was not statistically significant (P = .68). The median time to neutrophil and platelet recovery was 12 and 17 days, respectively. The CI of grade II acute graft-versus-host-disease (aGVHD) was 22% and 26% at 100 days and 6 months, respectively. The CI of chronic GVHD (cGVHD) was 7.5% at 3 years. There was no grade III or IV aGVHD, no severe cGVHD, and no deaths attributable to GVHD. In conclusion, the two-step approach HSCT demonstrated a low disease relapse rate and high survival in patients treated with 4 Gy TBI-based conditioning, despite a generally older and more medically compromised patient population., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Posttransplant cyclophosphamide (PtCy) has been shown to decrease post-hematopoietic stem cell transplant acute and chronic graft-versus-host disease (GVHD). In this study, PtCy was used in 44 patients along with mycophenolate and tacrolimus with HLA matched (29) and mismatched (15) unrelated donors to determine the impact of graft content on outcome; thus, all patients had flow cytometric analysis of their graft content including the number of B cells, NK cells, and various T cell subsets. Higher γδ T cell dose was associated with the development of acute GVHD (p = .0038). For PtCy, further studies of the cell product along with further graft manipulation, such as selective γδ T cell depletion, could potentially improve outcomes., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Abstract: Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received a single infusion of 1 of 4 escalating doses of a product containing 68.5% SARS-CoV-2-specific CD8+ CTLs/total cells. Symptom improvement and resolution in these patients was compared with an observational group of 18 patients lacking HLA-A∗02:01 who could receive standard of care. No dose-limiting toxicities were observed at any dosing level. Nasal swab polymerase chain reaction testing showed ≥88% and >99% viral elimination from baseline in all patients at 4 and 14 days after infusion, respectively. The CTLs did not interfere with the development of endogenous anti-SARS-CoV-2 humoral or cellular responses. T-cell receptor β analysis showed persistence of donor-derived SARS-CoV-2-specific CTLs through the end of the 6-month follow-up period. Interventional patients consistently reported symptomatic improvement 2 to 3 days after infusion, whereas improvement was more variable in observational patients. SARS-CoV-2-specific CTLs are a potentially feasible cellular therapy for COVID-19 illness. This trial was registered at www.clinicaltrials.gov as #NCT04765449., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary induction failure (PIF). Patients who received MAC allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After RIC allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1-3 cycles., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Contemporary, prospective data regarding the impact of granulocyte-colony stimulating factor (G-CSF) on outcomes after autologous hematopoietic stem cell transplantation (Auto-HSCT) in an era when stem cell grafts are more qualitatively robust are limited. Recent retrospective analyses have not supported a beneficial effect of post-transplantation G-CSF use on major outcomes after Auto-HSCT leading to strategies to delay or eliminate the use of G-CSF altogether in this context. To test the hypothesis that the infusion of consistently higher doses of stem cells (defined as ≥4 × 10 6 /kg) in Auto-HSCT will obviate the need for post-transplantation G-CSF. If so, the impact of withholding G-CSF will be noninferior to the use of G-CSF in terms of length of stay (LOS). The specific objectives were to conduct a prospective, randomized clinical trial primarily examining the impact of post-transplantation G-CSF on LOS, and secondarily on engraftment, infectious complications, antibiotic usage, and incidence of engraftment syndrome after Auto-HSCT in patients receiving versus not receiving G-CSF after Auto-HSCT. Patients with multiple myeloma or non-Hodgkin lymphoma (NHL) who underwent Pegfilgrastim plus Plerixafor-primed stem cell collection followed by Auto-HSCT were randomized to the G-CSF group (receive G-CSF starting at day 3 after Auto-HSCT) or the no G-CSF group (G-CSF withheld after Auto-HSCT). Seventy patients per arm were planned to demonstrate the primary endpoint of noninferiority in LOS between the G-CSF and the no G-CSF groups. Patient outcomes in the two groups were followed up and compared after Auto-HSCT, and an interim analysis for futility was planned when accrual reached 50%.The primary finding of this study was that despite only a 2-day longer median absolute neutrophil count (ANC) recovery in the no G-CSF arm (median 11 versus 13 days; P = .001), LOS was 4 days longer in patients not treated with G-CSF (median 11 days versus 15 days; P = .001). G-CSF use was associated with more robust incremental daily increases in ANC once recovered (P = .001), fewer days of febrile neutropenia (P = .001), and fewer days on antibiotics (P = .001), potentially contributing to this disproportionate finding. Inferiority in LOS in the no G-CSF group was demonstrated on the interim analysis, and the study was closed at the half-way point. There were no significant group differences in platelet recovery, documented infections, hospital readmissions, or overall survival at 1 year. Engraftment syndrome occurred in 54.3% of patients and was not related to G-CSF use. These results suggest that the increased LOS associated with the omission of G-CSF is largely due to concerns regarding the potential for infection in patients without a stable, recovered ANC in a hospital setting. Engraftment syndrome represented a significant source of febrile neutropenia further contributing to patient safety concerns and requires strategies to decrease its incidence. Infectious complications and death were not affected by the omission of G-CSF supporting a carefully monitored outpatient approach to Auto-HSCT in which white blood cell growth factor is eliminated or given as needed for documented infection. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the best curative option for the majority of patients with hematologic malignancies (HM); however, many elderly patients are excluded from transplant and outcome data in this population is still limited. The novel two-step graft engineering approach has been the main platform for allo-SCT at Thomas Jefferson University since 2006. Following administration of the preparative regimen, we infuse donor lymphocytes, followed by cyclophosphamide to induce bidirectional tolerance, then infusion of CD34-selected cells. A total of 76 patients ≥ 65 years old with HM underwent haploidentical (haplo) allo-SCT on the two-step transplant platform between 2007 and 2021. The median time to neutrophil engraftment was 11 days and platelet engraftment was 18 days. With a median follow up of 44 months, the 3-year overall survival (OS) and progression-free survival (PFS) were 36.3% and 35.6%, respectively. The cumulative incidences of non-relapse mortality (NRM) and relapse at 3 years were 43.5% and 21.0% at 3 years, respectively. The cumulative incidence of grade III-IV acute graft-versus-host-disease (GVHD) was 11.1% at 6 months, and chronic GVHD requiring treatment was 15.1% at 2 years. The two-step haplo allo-SCT is a novel alternative platform for high-risk older HM patients, achieving fast engraftment, low relapse rates and promising survival., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The 2-step graft engineering approach has been the main platform for allogeneic hematopoietic cell transplantation (allo-HCT) at Thomas Jefferson University since 2005. We have previously described separating donor lymphocyte infusion followed by cyclophosphamide for bidirectional tolerization from CD34-selected hematopoietic grafts in haploidentical and matched related donors. Here we analyzed 60 patients with high-risk lymphoid malignancies who underwent a 2-step allo-HCT between 2008 and 2020. The majority of patients received haploidentical stem cell grafts (82%), and 20% of patients received matched related donor stem cell grafts. The patients underwent allo-HCT for diffuse large C cell lymphoma (n = 17; 28%), chronic lymphoblastic leukemia (n = 10; 17%), follicular lymphoma (n = 8; 13%), and Hodgkin lymphoma (n = 7; 12%). Eight patients (13%) had received prior high-dose chemotherapy. Thirty patients (50%) had a Hematopoietic Cell Transplantation Comorbidity Index ≥3, and 20 patients (33%) had a Center for International Blood & Marrow Transplant Research Revised Disease Risk Index of high risk or very high risk. The median patient age was 56 years (range, 24 to 75 years). Neutrophils engrafted at a median of 11 days (range, 9 to 16 days), and platelets engrafted at a median of 16 days (range, 13 to 37 days). With a median follow-up of 6 years, the 3-year probability of overall survival was 62.9% (95% confidence interval [CI], 49.3% to 73.8%), and that of disease-free survival was 60.2% (95% CI, 46.4% to 71.6%). The cumulative incidence of relapse at 3 years was 11.9% (95% CI, 5.2% to 21.6%). The cumulative incidence of nonrelapse mortality at 3 years was 30.1% (95% CI, 1.91% to 42.0%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) at 1 year was 45% (95% CI, 32.2% to 57.0%), and that of grade III-IV acute GVHD at 1 year was 5% (95% CI, 1.3% to 12.6%). The cumulative incidence of cGVHD at 3 years was 15.2% (95% CI, 7.5% to 25.4%). The 2-step approach achieved excellent outcomes in high-risk lymphoid malignancies, with rapid neutrophil and platelet recovery., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with t-AML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT., (Copyright © 2021. Published by Elsevier Inc.)

The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P < .01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P < .01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR], .43; 95% confidence interval [CI], .24 to .78; P < .01) and PFS (HR, .43; 95% CI, .26 to .72; P < .01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)