-
1.
Pre-transplant glomerular hyperfiltration is not a risk factor for increased renal morbidity and mortality in pediatric stem cell transplant patients
Sarkar, N., Myers, K. C., Lane, A., Davies, S. M., Benoit, S. W.
Pediatric blood & cancer. 2024;:e30853
Abstract
Low glomerular filtration rate (GFR) prior to stem cell transplant (SCT) is associated with increased morbidity and mortality. The implications of abnormally high GFRs, or glomerular hyperfiltration, prior to SCT are unknown. Twenty-two of 74 consecutive pediatric SCT patients over 2 years old at a single center were hyperfiltrating prior to SCT, median nuclear medicine GFR 154 mL/min/1.73 m(2) [interquartile range: 146-170]. There was no association between hyperfiltration and any transplant demographics, nor between hyperfiltration and acute kidney injury (p = .8), renal replacement therapy (p = .63), 1-year event-free survival (p = 1), or abnormal creatinine-based estimated GFR at a median follow-up of 4.7 years (p = .73).
-
2.
Consenting rather than choosing. A qualitative study on overseas patients' decision to undergo hematopoietic stem cell transplantation
Sarradon-Eck, A., Franchina, L., Arnault, Y., Le Corroller, A. G., Zunic, P., Marino, P.
Cancer medicine. 2024
Abstract
OBJECTIVE Reasons for patients' acceptance of the allogeneic hematopoietic stem cell transplantation (allo-HSCT) proposed and how their decision may be affected by the long distances involved have not been sufficiently investigated so far. We therefore conducted a qualitative study to identify the factors involved in overseas patients' decision to accept allo-HSCT. METHODS In-depth semi-directive interviews were conducted with overseas allo-grafted patients (n = 22), as well as one non-consenting patient and their caregivers (n = 24). Interviews were analyzed taking an inductive thematic approach. RESULTS Respondents stated that their decision to undergo the transplantation was constrained by their feeling of being in a therapeutic impasse, the need for a survival strategy, the need to survive for their family's sake, family and doctors' pressures, and the feeling of being managed. The following factors favoring patients' acceptance were the medical information received, their faith, having a family donor, peer testimonies, and positive representations of the transplantation. Factors against patients' acceptance were geographical distance from home to the transplant center, apprehension of protective isolation, fear of dying, and representations of the graft. CONCLUSIONS These factors, such as patient's personal values and representations, need to be weighed up in order to adapt the information exchanged accordingly. Efforts are required to relieve patients' social isolation and improve the means of providing family support.
-
3.
[Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma]
Zhou, H. X., Jian, Y., Du, J., Liu, J. R., Zhang, Z. Y., Geng, C. Y., Yang, G. Z., Wang, G. R., Fu, W. J., Li, J., et al
Zhonghua nei ke za zhi. 2024;63(1):81-88
Abstract
Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.
-
4.
Early M-protein immune reconstitution after autologous haematopoietic stem cell transplantation is a good prognostic marker for patients with high-risk cytogenetic multiple myeloma
Zhu, H., Liu, J., Gu, J., Chen, M., Kuang, L., Huang, B., Zou, W., Li, J.
British journal of haematology. 2024
Abstract
The presence of transient abnormal protein banding (M-protein immune reconstitution) in serum immunofixation electrophoresis after autologous haematopoietic stem cell transplantation in patients with multiple myeloma has been reported. The purpose of this study was to investigate the impact of post-transplant M-protein immune reconstitution on the prognosis of patients with multiple myeloma. M-protein immune reconstitution was observed in 25.9% (75/290) of patients. The CR rate and MRD negativity were higher in the M-protein immune reconstitution group (85.3% vs. 69.3%, p = 0.013, 81.9% vs. 66.5%, p = 0.014). Although there were no significant differences between the groups, the overall median survival time was longer in the M-protein immune reconstruction group (80 vs. 72 m, p = 0.076; not reached vs. 105 m, p = 0.312). Among patients in the cytogenetic high-risk group, the occurrence of M-protein immune reconstitution predicted better PFS and OS (80 vs. 31 m, p = 0.010; not reached vs. 91 m, p = 0.026). Additionally, in revised-International Staging System stage III patients, PFS and OS were better in those who achieved M-protein immune reconstitution (80 vs. 20 m, p = 0.025; 57 vs. 32 m, p = 0.103). The better prognosis of M-protein immune reconstitution patients may be associated with the acquisition of a deeper response. In high-risk patients, early acquisition of M-protein immune reconstitution may suggest a better prognosis.
-
5.
Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation
Zhu, P., Yang, L., Wu, Y., Shi, J., Lai, X., Liu, L., Ye, Y., Yu, J., Zhao, Y., Yuan, X., et al
Clinical & translational immunology. 2024;13(1):e1484
Abstract
OBJECTIVE This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT). METHODS Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021. RESULTS A higher dose of graft CD8(+) T cells (≥ 0.85 × 10(8) kg(-1)) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; P = 0.002) and disease-free survival (DFS; HR, 1.751; P < 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; P = 0.038) and DFS (HR, 1.532; P = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8(+) T-cell risk system based on graft CD8(+) T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8(+) T-cell dose was negatively correlated with donor age (P < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (P < 0.001). CONCLUSION A higher CD8(+) T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.
-
6.
Efficacy and safety of letermovir prophylaxis for cytomegalovirus infection after hematopoietic stem cell transplantation
Li, W. W., Zhang, Y. M., Shen, M. Z., Mo, X. D.
Blood science (Baltimore, Md.). 2024;6(1):e00178
Abstract
Letermovir is a specific inhibitor of cytomegalovirus (CMV) terminase complex. Several studies have reported that letermovir can effectively prevent CMV activation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of letermovir prophylaxis for CMV infection after allo-HSCT with a systemic review and meta-analysis. A literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed and Embase databases were searched. A total of 28 studies were included. The incidence of CMV activation at 14 weeks after HSCT was 0.10 (95% confidence interval [CI], 0.06-0.18), which was 0.10 (95% CI, 0.04-0.21) and 0% in adult and children (2 studies were included and both of them were 0%). In addition, the incidence of CMV activation at 14 weeks after allo-HSCT was 0.11 (95% CI, 0.06-0.21) and 0.07 (only 1 study included), respectively, in retrospective and prospective studies. The incidence of CMV activation at 100 and 200 days after HSCT was 0.23 (95% CI, 0.16-0.33) and 0.49 (95% CI, 0.32-0.67), respectively. The incidence of CMV disease at 14 weeks and at 6 months after HSCT was 0.01 (95% CI, 0.01-0.02) and 0.03 (95% CI, 0.01-0.09), respectively. Thus, our systemic review and meta-analysis suggested that letermovir prophylaxis was safe and effective for CMV activation after allo-HSCT.
-
7.
Recruiting refugees and migrants as potential hematopoietic stem cell donors to serve patients of comparable ethnicities with rare human leucocyte antigen patterns - The BluStar.NRW project in North Western Germany
Heinemann, F. M., Baumgart, C., Binder, C., Börger, V., Fischer, J., Heinold, A., Jiménez Klingberg, C., Lenz, V., Riebschläger, S., Zeiler, T., et al
Transplant immunology. 2024;:101985
Abstract
Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.
-
8.
Characterization of the calcineurin inhibitor pain syndrome in patients undergoing allogeneic hematopoietic cell transplantation
Freyer, C. W., Carulli, A., Frey, N. V., Gill, S. I., Hexner, E. O., Martin, M. E., Luger, S. M., Porter, D. L., Stadtmauer, E. A., Loren, A. W.
Leukemia & lymphoma. 2024;65(2):250-256
Abstract
Calcineurin inhibitor pain syndrome (CIPS) is a rare complication of graft-vs-host disease prophylaxis following allogeneic hematopoietic cell transplant (alloHCT). CIPS presents as severe bilateral lower extremity pain, and the incidence, risk factors, and management of CIPS are poorly characterized.This is a single center retrospective study of patients who received tacrolimus (TAC) following alloHCT to describe the characteristics and management of CIPS and compare to a cohort who did not develop CIPS.Fifteen of 585 alloHCT patients (2.6%) developed CIPS at a median of 5 days following TAC initiation and a median level of 10.5 ng/mL. Severe bilateral foot, ankle, or leg pain were the primary symptoms. Patients with CIPS were younger and more frequently received myeloablative conditioning and total body irradiation compared to patients without CIPS. Analgesic regimens included dihydropyridine calcium channel blockers, gabapentinoids, topical diclofenac, and opioids.Clinicians should be aware of this uncommon but severe adverse effect.
-
9.
In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation
Leonard, A., Furstenau, D., Inam, Z., Luckett, C., Chu, R., Demirci, S., Essawi, K., Gudmundsdottir, B., Hinds, M., DiNicola, J., et al
Blood advances. 2024
Abstract
Stable, mixed donor-recipient chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with sickle cell disease (SCD) is sufficient for phenotypic disease reversal and results from differences in donor/recipient red blood cell (RBC) survival. Understanding variability and predictors of RBC survival among patients with SCD before and after HSCT is critical for gene therapy research which seeks to generate sufficient corrected hemoglobin to reduce polymerization thereby overcoming the red cell pathology of SCD. This study utilized biotin-labeling of RBCs to determine the lifespan of RBCs in patients with SCD compared to patients who have successfully undergone curative HSCT, participants with sickle cell trait (HbAS), and healthy (HbAA) donors (NCT04476277). Twenty participants were included in the analysis (N=6 SCD pre-HSCT, N=5 SCD post-HSCT, N=6 HbAS, N=3 HbAA). The average RBC lifespan was significantly shorter for participants with SCD pre-HSCT (64.1 days, range 35-91) compared to those with SCD post-HSCT (113.4 days, range 105-119), HbAS (126.0 days, range 119-147), and HbAA (123.7 days, range 91-147) (p<0.001). RBC lifespan correlated with various hematologic parameters, and strongly correlated with the average final fraction of sickled RBCs after deoxygenation (p<0.001). No adverse events were attributable to the use of biotin and related procedures. Biotin labeling of RBCs is a safe and feasible methodology to evaluate RBC survival in patients with SCD before and after HSCT. Understanding differences in RBC survival may ultimately guide gene therapy protocols to determine hemoglobin composition required to reverse the SCD phenotype as it relates directly to RBC survival.
-
10.
reduced Cytokine Release Syndrome and improved Outcomes with Earlier Immunosuppressive Therapy in Haploidentical Stem Cell Transplant
Tang, J., Jensen, R. R., Bryan, B., Hoda, D., Hunter, B. D.
Transplantation and cellular therapy. 2024
Abstract
BACKGROUND The optimal timing of immunosuppression and post-transplant cyclophosphamide (PTCy) in haploidentical stem cell transplant (haplo-HSCT) is not known. However, cytokine release syndrome (CRS) following haplo-HSCT is associated with worse transplant outcomes and the incidence of CRS may be affected by the timing of immunosuppression and PTCy. In this study, we compared CRS and other outcomes in 2 cohorts receiving different immunosuppression and PTCy schedules following haplo-HSCT. OBJECTIVE(S): In this study, we compared CRS and transplant outcomes in 2 cohorts receiving different immunosuppression and PTCy schedules following haplo-HSCT. STUDY DESIGN This is a retrospective cohort study of 91 patients who received haplo-HSCT at Intermountain Health Blood and Marrow Transplant Program. The original or standard haplo-HSCT GVHD prophylaxis regimen schedule included PTCy on days +3 and +4, with MMF and tacrolimus starting on day +5. The modified regimen adopted in November 2020, changed PTCy to days +3 and +5, with an earlier introduction of tacrolimus and MMF, starting on day -1 and 0 respectively. RESULT(S): Grade ≥ 1 CRS occurred in 32% of patients in the modified regimen, 82% in standard regimen (P < 0.0001), and 65% overall. Likewise, grade ≥ 2 CRS was lower with the modified regimen, 16% vs 57% (P = 0.0002). Mean duration of CRS symptoms lasted longer with the standard regimen, 3.14 days vs 1.44 days (P = 0.0003). Incidence of acute graft-versus-host disease (aGVHD) grades III-IV or extensive chronic GVHD (cGVHD) at 1 year was lower in the modified regimen 6% vs 32% (P = 0.0068). No differences were found in overall survival, relapse, or GVHD-free relapse-free survival (GRFS), although there appeared to be a trend towards improved GRFS in the modified regimen. Post-hoc analysis comparing GRFS in patients with and without CRS found that CRS was associated with lower GRFS at 1 year, 36% vs 63% (P = 0.0138). Days of broad-spectrum antibiotic therapy decreased by 7.5 days (P = 0.0017) and days to hospital discharge was reduced by 7.1 days (P = 0.0241) with the modified regimen. CONCLUSIONS This is the first analysis to evaluate and find a difference in CRS with early initiation of immunosuppressive therapy in haplo-HSCT. Our results suggest that this modified GVHD regimen benefits patients by reducing CRS and high grade GVHD compared to the standard PTCy-based GVHD prophylaxis regimen in haplo-HSCT. Additionally, this novel regimen did not appear to negatively impact outcomes.