-
1.
Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma
Giebel, S., Sobczyk-Kruszelnicka, M., Blamek, S., Saduś-Wojciechowska, M., Najda, J., Czerw, T., Mendrek, W., Woźniak, G., Jochymek, B., Radwan, M., et al
Bone marrow transplantation. 2021;56(6):1297-1304
Abstract
The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m(2) for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided "boosts" represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.
-
2.
Reduction of DMSO concentration in cryopreservation mixture from 10% to 7.5% and 5% has no impact on engraftment after autologous peripheral blood stem cell transplantation: results of a prospective, randomized study
Mitrus, I., Smagur, A., Fidyk, W., Czech, M., Prokop, M., Chwieduk, A., Glowala-Kosinska, M., Czerw, T., Sobczyk-Kruszelnicka, M., Mendrek, W., et al
Bone Marrow Transplantation. 2018;53(3):274-280
Abstract
The procedure of autologous peripheral blood stem cell transplantation (autoPBSCT) requires cryopreservation of cells in a mixture containing dimethyl sulfoxide (DMSO). DMSO is necessary to secure cell viability, however, its infusion may be toxic to stem cell recipient. The aim of this study was to prospectively evaluate the impact of DMSO concentration on engraftment after autoPBSCT. One-hundred-fifty patients were randomly assigned to one of three study arms; their leukapheresis products were cryopreserved in 10%, 7.5% or 5% DMSO. The study groups did not differ with regard to the diagnosis (mainly lymphomas and multiple myeloma), age, conditioning regimen, and the number of transplanted hematopoietic stem cells. 143 patients were treated with autoPBSCT. The frequency of adverse effects during and shortly after infusion was the lowest in 5% DMSO arm (p = 0.02 compared to 10% DMSO). 4 patients died due to infection before the engraftment. The median time to leukocyte and neutrophil recovery was 10 days in all study groups (p = 0.36 and p = 0.2). As well, the median day of platelet recovery was the same for all DMSO concentrations and equaled 15 days (p = 0.61).In view of these results, 5% DMSO mixture may be considered a new standard in cryopreservation of hematopoietic stem cells.
-
3.
Comparable safety profile of BeEAM (bendamustine, etoposide, cytarabine, melphalan) and BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning before autologous haematopoietic cell transplantation
Frankiewicz, A., Sadus-Wojciechowska, M., Najda, J., Czerw, T., Mendrek, W., Sobczyk-Kruszelnicka, M., Soska, K., Ociepa, M., Holowiecki, J., Giebel, S.
Contemporary oncology (Poznan, Poland). 2018;22(2):113-117
Abstract
Introduction: BEAM (carmustine, etoposide, cytarabine, melphalan) is the most frequently used high-dose chemotherapy regimen for patients with lymphoma referred for autologous haematopoietic cell transplantation (autoHCT). Recently, a novel conditioning protocol containing bendamustine instead of carmustine (BeEAM) has been proposed to potentially increase the efficacy. Aim of the study: The aim of this study was to retrospectively compare the safety profile of BEAM and BeEAM based on single-centre experience. Material and methods: A total of 237 consecutive patients with lymphoma treated with either BEAM (n = 174) or BeEAM (n = 63), between the years 2011 and 2016, were included in the analysis. Clinical characteristics of both groups were comparable. Patients with Hodgkin's lymphoma (HL) constituted 49% of the BEAM group and 40% of the BeEAM group. Results: Median time to neutrophil > 0.5 x 10(9)/l recovery was 10 days in both groups (p = 0.29), while median time to platelet > 50 x 10(9)/l recovery was 13 and 14 days after BEAM and BeEAM, respectively (p = 0.12). The toxicity profile was comparable except for arterial hypertension and severe hypokalaemia, which occurred more frequently after BeEAM compared to BEAM (p = 0.02 and p = 0.004, respectively). The rate of early mortality was 1.7% and 1.6%, respectively. The probabilities of the overall and progression-free survival were comparable for both groups (p = 0.73 and p = 0.55, respectively). Conclusions: Administration of bendamustine instead of carmustine as part of conditioning does not affect the engraftment or the toxicity profile of the regimen. Therefore, BeEAM may be safely used in patients with lymphoma undergoing autoHCT. Its efficacy requires evaluation in prospective studies.
-
4.
Increased efficacy of stem cell chemo-mobilization with intermediate-dose cytarabine plus G-CSF compared with G-CSF alone in patients with multiple myeloma: results of a randomized trial()
Czerw, T., Sadus-Wojciechowska, M., Michalak, K., Najda, J., Mendrek, W., Sobczyk-Kruszelnicka, M., Glowala-Kosinska, M., Chwieduk, A., Mitrus, I., Smagur, A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Mobilization of hematopoietic stem cells for patients with multiple myeloma (MM) may be done using either steady-state granulocyte colony-stimulating factor (G-CSF) or a combination of chemotherapy with G-CSF. The goal of this randomized, open label, phase 3 trial was to compare the efficacy of chemo-mobilization using intermediate-dose cytarabine (ID-AraC) plus G-CSF with G-CSF alone in MM patients referred for tandem autologous stem cell transplantation (autoSCT). The percentage of patients with stem cell yield of at least 5x10(6) CD34(+) cells/kg was the primary endpoint. Forty-six and 44 patients were assigned to ID-AraC arm and G-CSF arm, respectively. The threshold number of CD34(+) cells was reached in 43 (98%) patients in the ID-AraC group and 32 (70%) patients in the G-CSF arm (P=.0003). The median number of collected CD34(+) cells was 20.2 versus 5.9x10(6) cells/kg, respectively (P < .000001). A single apheresis was sufficient to achieve required number of harvested CD34(+) cells in 37 (86%) and 13 (41%) of cases, respectively (P=.00008). The time of both neutrophil and platelet recovery after autoSCT was significantly shorter for patients mobilized with ID-AraC. This study provides the first evidence for the advantage of chemo-mobilization over G-CSF monotherapy in terms of the efficacy. ID-AraC combined with G-CSF should be preferred among chemo-mobilization protocols for patients with MM planned for tandem autoSCT. This trial was registered at www.clinicaltrials.gov as #NCT01908621.
-
5.
Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission-Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: A retrospective study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Gorin, N. C., Labopin, M., Czerw, T., Pabst, T., Blaise, D., Dumas, P. Y., Nemet, D., Arcese, W., Trisolini, S. M., Wu, D., et al
Cancer. 2017;123(5):824-831
Abstract
BACKGROUND Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20%; P=.02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78%; P=.02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%. RESULTS Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2%; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49-0.87; P=.003) a better LFS (55.4% vs 44.6%; HR, 0.69; 95% CI, 0.53-0.89; P=.005), and a better OS (73.8% vs 63%; HR, 0.62; 95% CI, 0.47-0.82; P=.0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis; P=.01), and the LFS rate was 66% versus 47%, respectively (univariate analysis; P=.03). CONCLUSIONS In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017;123:824-31. © 2016 American Cancer Society. Copyright © 2016 American Cancer Society.
-
6.
Increased efficacy of intermediate-dose cytarabine + G-CSF compared to DHAP + G-CSF for stem cell mobilization in patients with lymphoma: an analysis by the polish lymphoma research group
Giebel, S., Sadus-Wojciechowska, M., Halaburda, K., Drozd-Sokolowska, J., Wierzbowska, A., Najda, J., Mendrek, W., Sobczyk-Kruszelnicka, M., Nowicki, M., Holowiecki, J., et al
Annals of Hematology. 2016;95(2):263-9
Abstract
Salvage regimens, like DHAP (dexamethasone, cytarabine, and cisplatin) are frequently used for stem cell mobilization in lymphoma. The aim of this study was to compare the efficacy of DHAP+G-CSF with intermediate-dose cytarabine (ID-AraC)+G-CSF, recently proposed as an alternative schedule. Consecutive patients with Hodgkin's or non-Hodgkin lymphoma who had received at least 2 lines of chemotherapy, mobilized with either DHAP (n=51) or ID-AraC (n=50)+G-CSF were included in the analysis. AraC was administered at the dose of 400 mg/m [1] bid intravenously for 2 days followed by filgrastim starting from day 5. In the AraC group, 96 % of patients collected at least 2x10 [2] CD34(+) cells/kg compared to 71 % in the DHAP group (p=0.0006). The CD34(+) cell yield was 9.3 (0-30.3)x10 [2]/kg vs. 5.6 (0-24.8)x10 [2]/kg, respectively (p=0.006). A single apheresis was sufficient to achieve the threshold number of CD34(+) cells in 82 % of the cases after AraC compared to 45 % after DHAP (p=0.001). We conclude that stem cell mobilization using ID-AraC is associated with a significantly higher efficacy than DHAP, allowing for collection of the transplant material in almost all patients with lymphoma. Our observation suggests that ID-AraC+G-CSF may be a preferable mobilization regimen in this setting.
-
7.
Long-term follow-up of patients with acute myeloid leukemia surviving and free of disease recurrence for at least 2 years after autologous stem cell transplantation: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Czerw, T., Labopin, M., Gorin, N. C., Giebel, S., Blaise, D., Meloni, G., Pigneux, A., Bosi, A., Veelken, J., Ferrara, F., et al
Cancer. 2016;122(12):1880-7
Abstract
BACKGROUND Leukemia recurrence is a major cause of treatment failure after autologous stem cell transplantation for acute myeloid leukemia (AML). It usually occurs within the first 2 years after transplantation. The goal of the current retrospective study was to assess the follow-up of and characterize risk factors for outcome among patients who survived free of disease recurrence after this period. METHODS The analysis included 3567 adults (median age, 45 years) with AML who underwent autografting during the first (86% of patients) or second (14% of patients) complete remission between 1990 and 2008. The stem cell source was the bone marrow in 32% of patients or the peripheral blood in 68% of patients. The median follow-up was 6.9 years. RESULTS At 5 years and 10 years after transplantation, the probability of leukemia-free survival was 86% and 76%, respectively; the recurrence incidence was 11% and 16%, respectively; and the nonrecurrence mortality rate was 3% and 8%, respectively. The observed survival was decreased compared with the expected survival of the general European population. In a multivariate analysis, decreased probability of leukemia-free survival was demonstrated for patients who underwent peripheral blood autologous stem cell transplantation; had French-American-British subtypes M0, M6, or M7; and were of an older age. The same factors were found to be associated with an increased risk of disease recurrence. Nonrecurrence mortality was found to be affected by older age. CONCLUSIONS The results of the current analysis indicate that late recurrences remain a major concern after autologous stem cell transplantation among patients with AML, indicating the need for close monitoring of minimal residual disease and additional leukemic control measures after transplantation. Cancer 2016;122:1880-7. © 2016 American Cancer Society. Copyright © 2016 American Cancer Society.