RESUMO

Posttransplant cyclophosphamide (PTCy) has practically revolutionized haploidentical (Haplo) hematopoietic cell transplantation (HCT). Comparisons between Haplo with PTCy and unrelated donor (URD) with conventional graft-versus-host disease (GVHD) prophylaxis have shown comparable overall survival with lower incidences of GVHD with Haplo/PTCy and led to the following question: is it PTCy so good that can be successfully incorporated into matched related donor (MRD) and URD HCT? In this review, we discuss other ways of doing PTCy, PTCy in peripheral blood haploidentical transplants, PTCy in the context of matched related and matched unrelated donors, PTCy with mismatched unrelated donors, and PTCy following checkpoint inhibitor treatment. PTCy is emerging as a new standard GVHD prophylaxis in haploidentical, HLA-matched, and -mismatched HCT.

Assuntos

Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Haploidêntico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doadores não Relacionados , Estudos Retrospectivos

RESUMO

BACKGROUND: Autologous stem cell transplantation is the standard procedure for multiple myeloma and the grafts are usually cryopreserved. Previous studies reported advantages in the use of fresh peripheral blood stem cells (PBSC) autotransplantation compared to cryopreservation of the grafts. This study compared the transplant-related outcomes of two graft preservation methods: fresh storage (4°C/72 h) and cryopreservation (-80°C). STUDY DESIGN AND METHODS: We performed an analysis of 45 patients with multiple myeloma under autotransplantation (17 fresh and 28 cryopreserved) from 2017 to 2021. Fresh PBSC were maintained in the refrigerator for three days in a concentration up to 300 × 103 TNC/µL. Cryopreserved PBSC were concentrated by plasma reduction after centrifugation (950 g/10 min/4°C) and an equal volume of cryoprotection solution was added for a final concentration of 300 × 103 TNC/µL, 5% DMSO, 6% hydroxyethyl starch, and 3% human albumin. RESULTS: Neutrophil engraftment was significantly faster with fresh PBSCs (10 vs. 11.5 days, p = 0.045). Adverse effects were more common in cryopreserved PBSC transplantation (75% vs. 35.3% patients; p = 0.013). Post transplantation hospital stay was 20 and 22 days for fresh and cryopreserved PBSCs respectively (p = 0.091). There was no difference in platelet engraftment time (10.5 days for both; p = 0.133), number of antibiotics used after transplantation (3 for fresh and 2.5 for cryopreserved; p = 0.828), days of antibiotic use after transplantation (12.2 days for fresh and 13.3 days for cryopreserved, p = 0.579), and overall survival (p = 0.736). CONCLUSION: The infusion of fresh PBSC refrigerated for up to three days is effective and safe for autologous transplantation in patients with multiple myeloma, which is a useful alternative to cryopreserved PBSC.

Assuntos

Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Células-Tronco de Sangue Periférico , Antibacterianos , Criopreservação/métodos , Dimetil Sulfóxido , Humanos , Mieloma Múltiplo/terapia , Albumina Sérica Humana , Amido , Transplante Autólogo/métodos

RESUMO

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for several malignant hematologic diseases and alternative donors, including haploidentical, play a significant role in HCT. Despite the increasing use of haplo-HCT with PTCy, some questions remain open. The objective of the present study was to investigate risk factors for adverse outcomes after haplo-HCT with PTCy. This is a retrospective study conducted at two Brazilian centers. A total of 103 patients with hematologic malignancies who underwent first allogeneic, haploidentical HCT with PTCy were included. Risk factors for death were age at transplant (HR = 1.03 for each year; p = 0.002) and high/very high disease risk index (DRI; HR = 2.77; p = 0.0007) and mother as the donor compared with other donors (HR = 3.53; p = 0.005). In multivariate analysis, PFS was significantly poorer for older patients (HR = 1.02; p = 0.006), high/very high DRI (HR = 2.39; p = 0.003), and mother as the donor compared with other donors (HR = 3.18; p = 0.006). Relapse rate was higher for high/very high DRI (HR = 4.01; p = 0.002) and mother as the donor compared with other donors (HR = 2.52; p = 0.05). NRM was higher for older patients (HR = 1.03 for each year; p = 0.03). Tacrolimus was a protective factor for grades II-IV aGVHD (HR = 0.46; p = 0.04) compared with cyclosporine. Peripheral blood (PBSC) was a risk factor for cGVHD (HR = 3.48; p = 0.006), while tacrolimus was protective (HR = 0.30; p = 0.009). Mother as the donor compared with other donors was also a risk factor for poorer OS, PFS, and relapse, suggesting that this combination should be avoided. Tacrolimus was protective for both grades II-IV aGVHD and cGVHD, suggesting that tacrolimus may be more effective than cyclosporine in preventing GVHD. PBSC was a risk factor for cGVHD without any impact on relapse. Prospective studies comparing tacrolimus with cyclosporine are awaited.

Assuntos

Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Ciclofosfamida/efeitos adversos , Ciclosporina , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva Local de Neoplasia/complicações , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Tacrolimo , Condicionamento Pré-Transplante/efeitos adversos

RESUMO

Abstract Introduction The isolation of captured peripheral blood mononuclear cells (PBMNCs) from leukoreduction filters (LRFs) can be of great importance in terms of bringing the lost cells back into use. Objective The aim of this study was to evaluate various methods based on their potential to recover the peripheral blood cells from LRFs with a focus on mononuclear cells (MNCs). Method For cell isolation from LRFs, three distinct methods (back-flushing, direct and vacuum pump) were compared through the calculation of the yield of isolated MNCs. The viability of extracted cells was determined by the flow cytometry technique. Moreover, the recovered MNCs were characterized regarding the presence of blood stem cell purification. The cell culture, microscopic observation, and immunophenotyping were employed to characterize the blood stem cells (hematopoietic, mesenchymal and progenitor endothelial stem cells). Results The yield of isolation obtained in the back-flushing, direct and vacuum pump methods were 17.7 ± 1.28, 17.3 ± 0.96 and 21.2 ± 0.90 percent, respectively. Although the highest potential for total blood cell recovery belonged to the vacuum pump method, the lowest cell viability (85.73 ± 4.84%) was observed in this method. However, the isolation process of the back-flushing and direct methods had less effect on cell viability. The characterization of the isolated MNCs displayed that the dominant positive phenotype was for CD34/CD45, indicating hematopoietic stem cells. In addition, the endothelial stem/progenitor cells were significantly detected as CD31/CD133 positive cells. Conclusion According to our results and considering the safety and efficiency potential of each of the applied methods, the back-flushing in comparison with the other methods can be considered a suitable procedure for MNC isolation from LRFs.

Assuntos

Leucócitos Mononucleares , Separação Celular , Células-Tronco de Sangue Periférico , Contagem de Células Sanguíneas , Citometria de Fluxo

RESUMO

INTRODUCTION: The isolation of captured peripheral blood mononuclear cells (PBMNCs) from leukoreduction filters (LRFs) can be of great importance in terms of bringing the lost cells back into use. OBJECTIVE: The aim of this study was to evaluate various methods based on their potential to recover the peripheral blood cells from LRFs with a focus on mononuclear cells (MNCs). METHOD: For cell isolation from LRFs, three distinct methods (back-flushing, direct and vacuum pump) were compared through the calculation of the yield of isolated MNCs. The viability of extracted cells was determined by the flow cytometry technique. Moreover, the recovered MNCs were characterized regarding the presence of blood stem cell purification. The cell culture, microscopic observation, and immunophenotyping were employed to characterize the blood stem cells (hematopoietic, mesenchymal and progenitor endothelial stem cells). RESULTS: The yield of isolation obtained in the back-flushing, direct and vacuum pump methods were 17.7 ±â€¯1.28, 17.3 ±â€¯0.96 and 21.2 ±â€¯0.90 percent, respectively. Although the highest potential for total blood cell recovery belonged to the vacuum pump method, the lowest cell viability (85.73 ±â€¯4.84%) was observed in this method. However, the isolation process of the back-flushing and direct methods had less effect on cell viability. The characterization of the isolated MNCs displayed that the dominant positive phenotype was for CD34/CD45, indicating hematopoietic stem cells. In addition, the endothelial stem/progenitor cells were significantly detected as CD31/CD133 positive cells. CONCLUSION: According to our results and considering the safety and efficiency potential of each of the applied methods, the back-flushing in comparison with the other methods can be considered a suitable procedure for MNC isolation from LRFs.