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1.
Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors
Jiang, B., Zhao, Y., Luo, Y., Yu, J., Chen, Y., Ye, B., Fu, H., Lai, X., Liu, L., Ye, Y., et al
Cell transplantation. 2024;33:9636897231225821
Abstract
KMT2A rearrangement (KMT2A-r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A-r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A-r and non-KMT2A-r cohorts, respectively. The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality rates of patients with KMT2A-r (n = 45) were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. Using propensity score matching, the 2-year OS rate of patients with KMT2A-r (n = 42) was lower than that of those without KMT2A-r (n = 42; 56.1% vs 88.1%, P = 0.003). Among patients with KMT2A-r (n = 45), the prognostic advantage was exhibited from transplantation in first complete remission (CR1) and measurable residual disease (MRD) negative, which was reflected in OS, RFS, and CIR (P < 0.001, P < 0.001, and P = 0.002, respectively). Furthermore, patients with AF6 had poorer outcomes than those with AF9, ELL, and other KMT2A-r subtypes (P = 0.032, P = 0.001, and P = 0.001 for OS, RFS, and CIR, respectively). However, no differences were found in the OS, RFS, and CIR between patients with KMT2A-r with and without mutations (all P > 0.05). Univariate and multivariate analyses revealed that achieving CR1 MRD negative before HSCT was a protective factor for OS [hazard ratio (HR) = 0.242, P = 0.007], RFS (HR = 0.350, P = 0.036), and CIR (HR = 0.271, P = 0.021), while AF6 was a risk factor for RFS (HR = 2.985, P = 0.028) and CIR (HR = 4.675, P = 0.004). The prognosis of patients with KMT2A-r AML was poor, particularly those harboring AF6-related translocation; however, it is not associated with the presence of mutations. These patients can benefit from achieving CR1 MRD negative before HSCT.
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2.
Disease Status and Interval between HCTs Predict Outcome of Pediatric Patients who Undergo a Subsequent HCT for Relapsed Hematologic Malignancy
Epperly, R., Li, Y., Selukar, S., Zeng, E., Madden, R., Mamcarz, E., Naik, S., Qudeimat, A., Sharma, A., Talleur, A., et al
Transplantation and cellular therapy. 2024
Abstract
BACKGROUND Patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplant (HCT) have a poor prognosis. While proceeding to subsequent HCT can provide potential for long-term survival, there is limited data to guide which patients are most likely to benefit and which HCT strategies are best in this heavily pre-treated population. OBJECTIVE The goals of this study were to: i) describe the clinical outcomes of a subsequent HCT in pediatric patients with relapsed hematologic malignancies in a cohort enriched for haploidentical donors, and ii) evaluate the association of patient-, disease-, and treatment-related factors with survival. STUDY DESIGN We retrospectively evaluated patients who underwent a subsequent HCT for management of post-HCT relapse at a single institution between 2000-2021. RESULTS Among 106 patients who received a second allogeneic HCT, one-year event-free survival (EFS) was 34% and one-year overall survival (OS) was 46%, with five-year EFS of 26% and five-year OS of 31%. Only disease-related factors were associated with outcome after second HCT, specifically the interval between HCTs and presence or absence of active disease at the time of HCT. In this cohort, patient- and treatment-related factors were not associated with differences in EFS or OS. Patients receiving a third or fourth HCT (n=13) had comparable survival outcomes to those receiving a second HCT. CONCLUSIONS Our experience highlights that a subsequent HCT has curative potential for a subset of patients who relapse after HCT, including those who receive a subsequent HCT from a haploidentical donor. While relapse and treatment-related toxicities remain major challenges, our study indicates that achieving complete remission prior to subsequent HCTs has the potential to further improve outcomes.
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3.
Prognostic value of ferritin in ASCT MM patients: integration with GEP models and ISS series systems
Guo, W., Zhan, Y., Mery, D., Siegel, E. R., Sun, F., Cheng, Y., Ashby, T. C., Zhang, Z., Bailey, C., Alapat, D. V., et al
Blood cancer journal. 2024;14(1):30
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4.
Intensified conditioning regimens with total marrow irradiation/etoposide/cyclophosphamide and busulfan/etoposide/cyclophosphamide overcome the impact of pre-transplant minimal residual disease on outcomes in high-risk acute lymphoblastic leukemia patients in complete remission
Zhao, X., Xu, Z., Li, Z., Zhou, X., Hu, Y., Wang, H.
Cancer medicine. 2024
Abstract
PURPOSE Among high-risk acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), those with positive minimal residual disease (MRD) are susceptible to poor outcomes. Therefore, it is necessary to determine the most suitable preparatory regimen for these patients. METHODS Data were analyzed from 141 patients who received allo-HSCT and were diagnosed with high-risk ALL. These patients underwent intensified conditioning regimens, including either total marrow and lymphoid irradiation (TMLI)-etoposide (VP16)-cyclophosphamide (CY) or busulfan (BU)-VP16-CY between October 2016 and November 2022. A total of 141 individuals were in complete remission (CR) before transplantation and, among all patients, 90 individuals exhibited a negative MRD status and 51 patients had a positive MRD status. RESULTS In patients who tested negative for MRD, the incidence of relapse within a 2-year timeframe was 25.0% (24.8%-25.5%), compared with 32.2% (31.2%-33.2%) in MRD-positive patients; however, this difference was not statistically significant. There were no significant differences in the 2-year disease-free survival (DFS) and 2-year overall survival (OS) rates between the MRD-negative and MRD-positive groups (DFS: 67.2% (57.9%-78.1%) vs. 55.5% (42.6%-72.3%); OS: 69.0% (61.9%-88.2%) vs. 66.7% (53.9%-82.5%)). Furthermore, no notable variations were observed in the occurrence of transplant-related mortality (TRM) and graft-versus-host disease (GVHD) across the two groups. CONCLUSION This study reveals the benefits of TMLI-VP16-CY and BU-VP16-CY conditioning regimens in high-risk ALL patients with CR and MRD-positive status. A large-scale prospective clinical trial is warranted in the future.
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5.
Autologous hematopoietic cell transplantation for T-cell prolymphocytic leukemia: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT
Drozd-Sokolowska, J., Gras, L., Koster, L., Martino, R., Salas, M. Q., Salmenniemi, U., Zudaire, T., Yañez, L., Bellido, M., Collin, M., et al
Haematologica. 2024
Abstract
Not available.
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6.
Nursing Experience in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia
Wu, X., Chao, J., Xu, Q.
Alternative therapies in health and medicine. 2024
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation stands as a vital treatment for leukemia, yet its implementation poses considerable challenges and complications. A comprehensive understanding of these challenges is crucial for appreciating the significance of enhanced nursing care. OBJECTIVE To explore and summarise the nursing experience of allogeneic haematopoietic stem cell transplantation for acute lymphoblastic leukaemia. The significance of this objective lies in the potential transformative impact that enhanced nursing care can have on overall patient outcomes within the context of allogeneic hematopoietic stem cell transplantation. METHODS Patients with acute lymphoblastic leukaemia treated with allogeneic haematopoietic stem cell transplantation in our hospital between August 2020 and January 2022 were recruited for this study. A total of 50 patients who met the complete inclusion criteria were enrolled and included in this study. Patients in the traditional group were given traditional nursing interventions, while patients in the exploration group were offered individualized interventions according to their personalized plans. In the traditional group, standard nursing care involved routine health education, vital signs monitoring, and sterile care in a laminar flow ward. Post-transplantation changes were observed, and patients were encouraged to engage in suitable exercises. The exploration group received enhanced infection control measures, including regular disinfection and cleaning of patient wards. Individualized care plans, collaborative chemotherapy consultations, and extensive patient and family education were implemented. Clinical data of all patients were collected, and their nursing experience was summarized and analyzed by comparing the incidence of adverse reactions and evaluating nursing satisfaction. RESULTS The analysis group demonstrated a significantly lower incidence of adverse reactions compared to the traditional group. Specifically, the total adverse reaction rate in the analysis group was 8.00%, markedly lower than the traditional group's 48.00% (P < .05). Moreover, patient satisfaction in the exploration group was significantly higher than that observed in the traditional group (P < .05). In detail, the satisfaction level in the exploration group reached 92.67%, while the traditional group reported a satisfaction level of 77.56%. CONCLUSION For patients with acute lymphoblastic leukaemia who received allogeneic haematopoietic stem cell transplantation, a personalized care intervention plan involving careful primary nursing, full protection and enhanced psychological care can It can effectively improve the adverse effects of sleep, thus increasing their satisfaction with nursing.
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7.
Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma
Xin, X., Lin, L., Yang, Y., Wang, N., Wang, J., Xu, J., Wei, J., Huang, L., Zheng, M., Xiao, Y., et al
Cytotherapy. 2024
Abstract
BACKGROUND AIMS The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown. METHODS In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively. RESULTS The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders). CONCLUSIONS For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.
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8.
Early Impact of Mobilization Process on Cardiac Function and Size in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation
Vaitiekiene, A., Kulboke, M., Bieseviciene, M., Bartnykaite, A., Kireilis, B., Rinkuniene, D., Jankauskas, A., Zemaitis, J., Gaidamavicius, I., Gerbutavicius, R., et al
Journal of clinical medicine. 2024;13(3)
Abstract
Background: The hematopoietic stem cell transplantation (HSCT) process is known to cause cardiac toxicity of different grades. In this paper, we aimed to evaluate the impact of mobilization procedure of hematopoietic stem cells for autologous HSCT process for left and right ventricle sizes and functions. Material and Methods: The data of 47 patients undergoing autologous HSCT were analyzed. All patients underwent hematopoietic stem cell mobilization with chemotherapy and filgrastim at 10 µg/kg/d. Echocardiography was performed two times: before enrolling in the transplantation process and after mobilization before the conditioning regimen for transplantation. Changes in left and right ventricle (RV) diameter and systolic and diastolic function of the left ventricle and systolic function of the RV were measured. Results: A statistically significant difference was observed in the change of right ventricular function (S')-it slightly decreased. Mean S' before mobilization was 13.93 ± 2.85 cm/s, and after mobilization it was 12.19 ± 2.64 cm/s (p = 0.003). No statistically significant change in left ventricular diameter and systolic and diastolic function and RV diameter was observed. Conclusions: The mobilization procedure in patients undergoing autologous HSCT is associated with reduced RV systolic function. S' could be used as a reliable tool to evaluate early cardiotoxicity in HSCT patients and guide further follow-up.
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9.
Gemcitabine-based conditioning compared to BEAM/BEAC conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: No difference in outcomes
Liu, H., Zou, H., Shan, D., Liu, W., Huang, W., Sui, W., Deng, S., Wang, T., Lv, R., Fu, M., et al
Cancer medicine. 2024;13(2):e6965
Abstract
BACKGROUND High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL. METHODS A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results. RESULTS Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC). CONCLUSIONS The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.
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10.
Haploidentical Transplant with Post-Transplant Cyclophosphamide for Acute Myeloid Leukaemia and Myelodysplastic Syndromes Patients: The Role of Previous Lines of Therapy
Avenoso, D., Serpenti, F., Slonim, L. B., Bouziana, S., Dazzi, F., Hannah, G., Kenyon, M., Mehra, V., Kulasekararaj, A., Krishamurthy, P., et al
Mediterranean journal of hematology and infectious diseases. 2024;16(1):e2024002
Abstract
BACKGROUND Allogeneic haematopoietic stem-cell transplant is an option, potentially curative, for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Post-transplant cyclophosphamide administration allows for the selection of haploidentical donors in patients who are eligible for the procedure but do not have a fully matched donor since it can overcome the HLA barrier. There is still an active debate on whether intensifying the conditioning regimen is necessary with haploidentical donors when peripheral blood stem cells are used as the graft source. Herein, we report our decennial experience of haploidentical stem-cell transplant using peripheral blood stem cells (haplo-PBSC) at King's College Hospital. OBJECTIVES The primary objective was to evaluate overall survival (OS) following haplo-PBSC. Secondary objectives were total OS for patients with less than two previous lines of therapy, OS according to cytomegalovirus (CMV) reactivation, incidence of transplant-related mortality (TRM), graft-versus-host disease (GVHD) and GVHD-relapse-free survival (GRFS). RESULTS One-year and three-year total OS were 62% and 43%, respectively, with a median OS of 22 months. One-year and three-year OS for patients with ≤2 and those with >2 previous lines of therapy were 72% and 55%, and 60% and 22%, respectively (p-value=0.04). The median OS in patients with >2 previous and ≤2 lines of therapy was 16 and 49 months, respectively. Cumulative incidence (CI) of relapse was 25% with a median time to relapse of 5 months (range 1 - 38 months). CONCLUSIONS Haploidentical haematopoietic stem-cell transplant is potentially curative in chemosensitive AML and MDS and offers a high rate of prolonged remission. Our cohort further confirms the role of consolidative haploidentical transplant in patients in complete remission and highlights that patients with heavily pre-treated disease may not benefit from this strategy.