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1.
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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2.
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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3.
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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4.
A machine-learning model that incorporates CD45 surface expression predicts hematopoietic progenitor cell recovery after freeze-thaw
Al-Riyami, A. Z., Maryamchik, E., Hanna, R. S., Pashmineh Azar, A. R., Zheng, X., Choudhari, S., Finn, C., Giacobbe, N., Machietto, R., Rieser, R., et al
Cytotherapy. 2023;25(10):1048-1056
Abstract
BACKGROUND AIMS Sufficient doses of viable CD34+ (vCD34) hematopoietic progenitor cells (HPCs) are crucial for engraftment. Additional-day apheresis collections can compensate for potential loss during cryopreservation but incur high cost and additional risk. To aid predicting such losses for clinical decision support, we developed a machine-learning model using variables obtainable on the day of collection. METHODS In total, 370 consecutive autologous HPCs, apheresis-collected since 2014 at the Children's Hospital of Philadelphia, were retrospectively reviewed. Flow cytometry was used to assess vCD34% on fresh products and thawed quality control vials. The ratio of vCD34% thawed to fresh, which we call "post-thaw index," was used as an outcome measure, with a "poor" post-thaw index defined as <70%. HPC CD45 normalized mean fluorescence intensity (MFI) was calculated by dividing CD45 MFI of HPCs to the CD45 MFI of lymphocytes in the same sample. We trained XGBoost, k-nearest neighbor and random forest models for the prediction and calibrated the best model to minimize falsely-reassuring predictions. RESULTS In total, 63 of 370 (17%) products had a poor post-thaw index. The best model was XGBoost, with an area under the receiver operator curve of 0.83 evaluated on an independent test data set. The most important predictor for a poor post-thaw index was the HPC CD45 normalized MFI. Transplants after 2015, based on the lower of the two vCD34% values, showed faster engraftment than older transplants, which were based on fresh vCD34% only (average 10.6 vs 11.7 days, P = 0.0006). CONCLUSIONS Transplants taking into account post-thaw vCD34% improved engraftment time in our patients; however, it came at the cost of unnecessary multi-day collections. The results from applying our predictive algorithm retrospectively to our data suggest that more than one-third of additional-day collections could have been avoided. Our investigation also identified CD45 nMFI as a novel marker for assessing HPC health post-thaw.
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5.
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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6.
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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7.
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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8.
Long-term outcome of immunologic autograft engineering
Porrata, L. F., Inwards, D. J., Ansell, S. M., Micallef, I. N., Johnston, P. B., Villasboas, J. C., Paludo, J., Markovic, S. N.
EJHaem. 2022;3(2):488-491
Abstract
Our phase III trial reported that autograft-absolute lymphocyte count (A-ALC) improved survival post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) for a short-term follow-up of 2 years. We evaluated retrospectively in our phase III trial patients that the A-ALC still confers survival benefit with a longer follow-up. With a median follow-up of 127.6 months, patients infused with an A-ALC ≥ 0.5 × 10(9) cells/kg experienced better overall survival (HR = 0.392, 95% confidence of interval [CI]: 0.224-0.687, p < 0.001) and progression-free survival (HR = 0.413, 95% CI: 0.253-0.677), p < 0.0004). This study supports that A-ALC provides long-term survival benefit post APBHSCT.
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9.
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.
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10.
Autologous hematopoietic cell transplantation for relapsed multiple myeloma performed with cells procured after previous transplantation-study on behalf of CMWP of the EBMT
Drozd-Sokołowska, J., Gras, L., Zinger, N., Snowden, J. A., Arat, M., Basak, G., Pouli, A., Crawley, C., Wilson, K. M. O., Tilly, H., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse.
PICO Summary
Population
Patients with multiple myeloma who relapsed after first autologous stem cell transplant (n=305)
Intervention
Stem cell remobilisation and autologous stem cell transplant (auto-HCT)
Comparison
None
Outcome
The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS.