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1.
Dual T cell depletion for graft versus host disease prevention in peripheral blood haploidentical hematopoietic cell transplantation for adults with hematological malignancies
Alfaro Moya, T., Salas, M. Q., Santos Carreira, A., Atenafu, E. G., Law, A. D., Lam, W., Pasic, I., Kim, D. D. H., Michelis, F. V., Novitzky Basso, I., et al
Bone marrow transplantation. 2024
Abstract
The ideal immunosuppressive agents to complement post-transplant cyclophosphamide (PTCy) in PBSC-based haploidentical hematopoietic cell transplantation (haplo-HCT) remain debated. This study looks at our experience with ATG-PTCy-Cyclosporine (CsA) prophylaxis in PB haplo-HCT since 2015. Between October 2015 and December 2021, 157 adults underwent haploidentical hematopoietic cell transplantation (haplo-HCT) using a GVHD prophylaxis regimen comprising rabbit-ATG, PTCy, and CsA. Among these patients, 76.4% received a total ATG dose of 4.5 mg/kg, and 23.5% received 2 mg/kg. T-cell replete peripheral blood stem cell (PBSC) grafts were infused on day 0. The study reported a median follow-up of 32 months (range 0.3-61.64) for survivors. The cumulative incidence of grade II-IV and grade III-IV acute GVHD at day +100 was 26.3% and 9.5%, respectively. Moderate/severe chronic GVHD at 1 year was 19.9%. The 2-year overall survival (OS) was 49.4%, with a relapse-free survival (RFS) of 44.6%. In multivariate analysis, older patients, and those with high/very-high disease risk indices (DRI) were at higher risk for worse OS and higher non-relapse mortality (NRM). The study confirms that using PTCy and ATG (4.5 mg/kg), alongside CsA is safe and effective in preventing GVHD when using peripheral blood as the stem cell source in haploidentical hematopoietic cell transplantation (haplo-HCT).
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2.
A critical assessment of dose effects of post-thaw CD34 on autologous stem cell transplantation treatment of haematological malignancies
Duarte, G. C., Butler, A., Atkinson, G., Badami, K., Wei, W. H.
EJHaem. 2023;4(2):419-427
Abstract
A consensus threshold of pre-cryopreservation CD34-positive cells (CD34s) has been used as the minimum dose to initiate autologous stem cell transplantation (ASCT). Advances in cryopreservation posed a debate whether post-thaw CD34s might be a superior surrogate instead. We addressed the debate in this retrospective study of 217 adult ASCTs in five different haematological malignancies treated at a single centre. We showed that post-thaw CD34s was highly correlated with pre-cryopreservation CD34s (r = 0.97) and explained ∼2.2% (p = 0.003) of the variation of the post-thaw total nucleated cell viability that however had no power to predict engraftment outcomes. After stratifying the ASCT cases into four dose groups based on post-thaw CD34s reinfused, stepwise multivariate regression analyses detected significant effects in dose group and interactions with diseases for neutrophil and platelet recovery respectively. The significant dose effects and interactions were triggered by two technical outliers in the low dose group, and disappeared in the repeated regressions after exclusion of the outliers where disease and age were the significant predictors remained. Our data clearly support the validity of the consensus threshold in ASCT applications but also highlight neglected conditions where monitoring post-thaw CD34s and clinical attributes are valuable.
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3.
Efficacy of ex vivo purging with CD34+ selection to maximize the effects of autologous stem cell transplantation in peripheral T-cell lymphoma patients
Jeon, Y., Kim, T. Y., Min, G. J., Park, S. S., Park, S., Yoon, J. H., Lee, S. E., Cho, B. S., Eom, K. S., Kim, Y. J., et al
Cytotherapy. 2023
Abstract
BACKGROUND AIMS Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.
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4.
Cryopreservation and storage patterns of hematopoietic progenitor stem cells for multiple myeloma
Benjamin, C. L., Desai, S., Pereira, D., Beitinjaneh, A., Jimenez, A., Goodman, M., Lekakis, L., Spiegel, J., Komanduri, K. V., Wang, T. P.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103731
Abstract
Autologous hematopoietic stem cell transplantation (HCT) has been a standard of care treatment for eligible patients with newly diagnosed multiple myeloma (MM). Guidelines generally recommend hematopoietic progenitor cell (HPC) harvest for two potential HCT. There is a paucity of data reporting use of such collections in the era of novel approved therapies. In this single-center retrospective study, our goal was to determine the HPC utilization rate and costs associated with leukocytapheresis, collection, storage, and disposal to guide future HPC collection planning. We included 613 patients with MM who underwent HPC collection over a nine-year period. The patients were separated into four groups based on HPC utilization: 1) patients who never proceeded to HCT, or Harvest and Hold (14.8 %), 2) patients who proceeded to one HCT with banked HPC remaining (76.8 %), 3) patients who proceeded to one HCT without HPC remaining (5.1 %), and 4) patients who proceeded to two HCTs (3.3 %). After collection, 73.9 % of patients underwent HCT within 30 days. Of patients with banked HPC, defined as not undergoing HCT within 30 days of leukocytapheresis, the overall utilization rate was 14.9 %. At 2- and 5-years post HPC collection, utilization rate was 10.4 % and 11.5 %, respectively. In conclusion, our results suggest very low utilization of stored HPC, raising into question the current HPC collection targets. Given advances in MM therapy, as well as significant costs associated with harvest and storage, collection for unplanned future use warrants reconsideration. As a result of our analysis, our institution has reduced our HPC collection targets.
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5.
Non-Cryopreserved Peripheral Blood Stem Cell Graft for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma and Lymphoma Patients
Noiperm, P., Julamanee, J., Viboonjuntra, P., Lekhakula, A.
Annals of transplantation. 2023;28:e938595
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) using cryopreserved grafts is time-consuming, expensive treatment, and may associated with dimethyl sulfoxide (DMSO) toxicity. Here, we assess the clinical utility and safety of non-cryopreserved peripheral blood stem cell graft in autologous HSCT. MATERIAL AND METHODS Medical data of multiple myeloma or lymphoma patients who underwent autologous non-cryopreserved HSCT were reviewed. RESULTS A total of 58 patients (40 myeloma and 18 lymphoma) were reviewed. The median myeloma and lymphoma CD34⁺ cell doses were 7.59 and 6.9 million/kg, respectively, with good viability after storage. The median times in neutrophil and platelet engraftment were 9 and 13 days and 11 and 14 days in myeloma and lymphoma, respectively. Only 5 patients in this cohort developed serious post-transplant complications. After transplantation, the cumulative incidence of relapse at 5 years was 34.4% in myeloma versus 19.1% in lymphoma patients. Notably, the mortality incidence rate rapidly increased within the first year and reached a plateau after 4 years, with cumulative incidence of 5.9% and 30.9% in myeloma and lymphoma, respectively. With a median follow-up time of 60 months, the median progression-free survival (PFS) and overall survival (OS) for lymphoma patients was 123.8 and 130 months, respectively. For the myeloma group, the median follow-up time was 38.6 months, the median PFS was 99.5 months, and OS was 157 months. CONCLUSIONS Non-cryopreserved HSCT is effective and safe. The long-term survival outcomes could be achieved by the shortening the duration of neutrophil and platelet engraftments and the complication rates are acceptable.
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6.
Autologous Stem Cell Transplant in Lymphoma Using a Noncryopreserved Platform: An Adapted Sequential Conditioning Maintaining Dose Intensity Does not Affect Transplantation Outcomes
Sarmiento, M., Rojas, P., Gutierrez, C., Quezada, J., Jara, V., Campbell, J., Maria, G., Jose,, VicenteSandoval,, Vergara, M., et al
Clinical lymphoma, myeloma & leukemia. 2023
Abstract
BACKGROUND Hematopoietic autologous stem cell transplantation (ASCT) is a validated therapeutic strategy for lymphoma treatment and precise well-tolerated conditioning. Several conditioning methods are available, but the most commonly used are CVB, BEAM, and ICE, which are conventionally administered in 6 to 7 days. Since 2015, our program has moved toward noncryopreserved platforms that require concise times; therefore, we have modified the conditioning by reducing it to 4 to 5 days. In this study, we show our experience. METHODS We compared ASCT performed in our program before and after 2015 in lymphoma patients. Between 2000 and 2014 and from 2015 to 2022, we performed 46 and 61 ASCT procedures, respectively. RESULTS Since 2015, we observed a greater number of infused stem cells, fewer episodes of febrile neutropenia (60% vs. 37% P = .008), shorter hospitalizations (30 vs. 18 days P = .001), faster engraftment (20 vs. 14 days P = .001) and better progression-free survival (72 vs. 44 months P = .002). Additionally, a prolonged overall survival was observed at these results, and this prolonged survival is difficult to interpret due to the short follow-up. CONCLUSION In conclusion, conditioning adjusted for a noncryopreserved strategy offers at least similar or even better results than the cryopreserved strategy. Prospective studies are warranted.
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7.
Trends in utilization of stored cryopreserved autologous peripheral hematopoietic cells intended for a second (or beyond) autologous hematopoietic cell transplantation in patients with multiple myeloma: a single center experience
Yassine, F., Kharfan-Dabaja, M. A., Tsalantsanis, A., Roy, V., Zubair, A. C., Murthy, H. S., Ayala, E., Iqbal, M., Sher, T., Ailawadhi, S., et al
Bone marrow transplantation. 2023
Abstract
Due to the advent of effective novel therapies for multiple myeloma (MM), the use of cryopreserved autologous peripheral blood hematopoietic cells (APBHC) for a salvage autologous transplant (auto-HCT) is in decline. We evaluated utilization trends and costs associated with cryopreserved APBHC in patients with MM. We retrospectively evaluated the clinicopathologic data from 440 patients with MM who underwent APBHC mobilization and collection at Mayo Clinic Florida between 2010 and 2019. Based on institution-specific charges as of May 2021, the cost of 1 session of APBHC collection/apheresis was $4,680 and the cost of 1 year of APBHC cryopreservation was $4,790 per patient. Out of 347 patients who had APBHC in cryopreservation, 5 (1.4%) underwent a salvage auto-HCT and 61% of patients had ≥1 excess collection sessions for APBHC that ultimately went unused. The median cost of excess collection sessions was $4,680 per patient (range, $4,680-$32,760) and the median total cost for excess collection sessions plus costs for storage was $23,840 per patient (range, $4,680-$85,450). The sum of costs of excess collection sessions was $2,077,920 and the sum of costs of cryopreservation was $5,812,665. Institutional policies regarding universal APBHC collection and long-term storage should be reevaluated in the era of novel therapeutics.
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8.
TCRαβ/CD19 cell-depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis
Merli, P., Algeri, M., Galaverna, F., Bertaina, V., Lucarelli, B., Boccieri, E., Becilli, M., Quagliarella, F., Rosignoli, C., Biagini, S., et al
Blood. 2023
Abstract
TCRαβ/CD19-cell depletion is a promising graft manipulation technique frequently used in the context of HLA-haploidentical hematopoietic stem cell transplantation (HSCT). We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of this type of ex-vivo T cell-depletion in 80 children with acute leukemia, showing promising survival outcomes. We now report an updated analysis on a cohort of 213 children with a longer follow-up (median value of 47.6 months for surviving patients). With a 5-year cumulative incidence of non-relapse mortality of 5.2% (95% confidence interval, CI, 2.8-8.8) and a cumulative incidence of relapse of 22.7% (95% CI, 16.9-29.2), projected 10-year overall and disease-free survival (DFS) were 75.4% (95% CI 68.6-80.9) and 71.6% (95% CI 64.4-77.6), respectively. Cumulative incidence of both grade II-IV acute and chronic GvHD were low (14.7% and 8.1%, respectively). In a multivariable analysis for DFS including also type of disease, use of total body irradiation in the conditioning regimen [hazard ratio (HR) 0.5 (95% CI, 0.26-0.98, p=0.04)], disease status at HSCT [CR>3 versus CR1/2; HR 2.23 (95% CI, 1.20-4.16, p=0.01] and high levels of pre-HSCT minimal residual disease [HR 2.09 (95% CI, 1.01-4.33, p=0.04)] were independently associated with outcome. In summary, besides confirming the good outcome results already reported (which are almost superimposable to those of transplant from HLA-matched donors), this clinical update allows the identification of patients at higher risk of treatment failure for whom personalized approaches, aimed at reducing the risk of relapse, are warranted.
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9.
Loss of CD34(+) Cells and Effect of the Number of Viable Cryopreserved CD34(+) Cells in the Infused Blood Grafts on Hematologic Recovery, Progression-Free Survival and Overall Survival in NHL Patients After Autologous Stem Cell Transplantation
Partanen, A., Turunen, A., Valtola, J., Pyörälä, M., Kuittinen, O., Kuitunen, H., Vasala, K., Penttilä, K., Kuittinen, T., Mäntymaa, P., et al
Clinical lymphoma, myeloma & leukemia. 2023
Abstract
PATIENTS This post-hoc study aimed to find out factors affecting graft viable CD34(+) cell loss during processing and cryopreservation in 129 non-Hodgkin lymphoma (NHL) patients receiving autologous stem cell transplantation (auto-SCT) and the impact of a low (< 2.0 × 10(6)/kg, group A) and a decent number (≥ 2 × 10(6)/kg, group B) of viable CD34(+) cells infused on the hematologic recovery, progression-free survival (PFS) and overall survival (OS) after auto-SCT. RESULTS The median loss of viable CD34(+) cells during cryopreservation was higher in group A (47% vs. 19%, p < .001). A higher yield of CD34(+) cells at the first apheresis in group B (p = .002) was linked with greater loss of viable graft CD34(+) cells after cryopreservation. Filgrastim (FIL) use for mobilization seemed to associate with higher viable CD34(+) cell loss compared to pegfilgrastim (PEG) or lipegfilgrastim (LIPEG) in both groups (in group A FIL 66 vs. PEG 35%, p = .006; in group B FIL 37 vs. PEG 15 vs. LIPEG 13%, p < .001). Hematologic recovery after auto-SCT was faster in group B. Neither viable CD34(+) cell loss during storage nor viable CD34(+) cell number < 2.0 × 10(6)/kg infused affected on PFS or OS. CONCLUSIONS G-CSF type used in mobilization and mobilization capacity were found to correlate with viable CD34(+) cell loss during processing and storage. Most importantly, low infused viable CD34(+) cell count did not seem to impact on PFS or OS.
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10.
Effect of nucleated cell count and cryopreservation on engraftment post autologous stem cell transplant
Welschinger, L., Milton, C., Zaunders, G., Ashraf, A.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2022;61(6):103495
Abstract
Using 753 collections from 426 adult haematology patients, we conducted a retrospective, analysis into the effects of overnight storage and nucleated cell counts (NCC) on viable, CD34(+) (vCD34(+)) recovery and engraftment kinetics post autologous stem cell, transplant (ASCT) with peripheral blood stem cells (PBSC). There were significant, differences in vCD34 + recovery ( P < 0.01) after cryopreservation associated with, the fresh NCC of ≥ 300 × 10 (6) /mL in products stored overnight, but no association, with time to platelet or neutrophil engraftment post-ASCT was observed for these, products. There was no association of vCD34(+) numbers or engraftment kinetics with cryopreserved NCC with either below or greater than the local recommended concentration of 400 × 10(6) /mL of product. However, there was significant difference in engraftment kinetics in relation to the viable CD34(+) dose given at ASCT, in relation to the time to early engraftment and the amount of platelet support given during the engraftment period post-ASCT. We conclude the vCD34(+) dose at ASCT is of great importance to early engraftment kinetics and that NCC is an important factor during overnight storage, but not for cryopreservation of PBSC. In light of our findings, we recommend that apheresis products collected in a closed system can safely be stored undiluted overnight.