Donor source and post‐transplantation cyclophosphamide influence outcome in allogeneic stem cell transplantation for GATA2 deficiency

Author(s):  
Diana X. Nichols‐Vinueza ◽  
Mark Parta ◽  
Nirali N. Shah ◽  
Jennifer M. Cuellar‐Rodriguez ◽  
Thomas R. Bauer ◽  
...  
Author(s):  
Steffen T. Simon ◽  
Anne Pralong ◽  
Michael Hallek ◽  
Christoph Scheid ◽  
Udo Holtick ◽  
...  

AbstractPatients undergoing allogeneic stem cell transplantation (allo-SCT) are given a real chance of cure, but at the same time are confronted with a considerable risk of mortality and of severe long-term impediments. This narrative, non-systematic literature review aims to describe the supportive and palliative care needs of allo-SCT recipients, including long-term survivors or those relapsing or dying after transplantation. It also evaluates the feasibility and effectivity of integrating palliative care early in transplant procedures. In this appraisal of available literature, the main findings relate to symptoms like fatigue and psychological distress, which appear to be very common in the whole allo-SCT trajectory and might even persist many years post-transplantation. Chronic GvHD has a major negative impact on quality of life. Overall, there is a paucity of research on further issues in the context of allo-SCT, like the distress related to the frequently unpredictable post-transplant trajectory and prognosis, as well as the end-of-life phase. First randomized controlled results support the effectiveness of early integration of specialized palliative care expertise into transplant algorithms. Barriers to this implementation are discussed.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6533-6533
Author(s):  
Satoshi Nishiwaki ◽  
Koichi Miyamura ◽  
Kazuteru Ohashi ◽  
Mineo Kurokawa ◽  
Shuichi Taniguchi ◽  
...  

6533 Background: Although allogeneic stem cell transplantation (allo-SCT) could improve the outcome of adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL], the impact of the donor source, particularly the position of cord blood (CB) transplantation, is still uncertain. Methods: We retrospectively analyzed 1726 adult Ph(-) ALL patients transplanted at the first time between 1998 and 2009 with myeloablative preparative regimens who were registered in the Japan Society for Hematopoietic Cell Transplantation database. Two hundred and thirty-three received CB transplantation [first complete remission (CR1): 95, subsequent CR: 53, non-CR: 85], 809 received allo-SCT from unrelated donor (URD) (CR1: 434, subsequent CR: 158, non-CR: 217), and 684 received allo-SCT from related donor (RD) (CR1: 388, subsequent CR: 89, non-CR: 207). Results: Overall survival (OS) in patients after CB transplantation in CR1 was comparable with that after allo-SCT from URD or RD [57% in CB, 64% in URD, and 65% in RD at 4 years, respectively, P=0.11]. Donor source was not a significant risk factor for OS in multivariate analysis. Although URD was a favorable factor for relapse and an unfavorable factor for non-relapse mortality (NRM), CB was not a significant factor for them [Relapse: 22% in CB, 17% in URD, and 24% in RD at 3 years, respectively (P=0.02); NRM: 27% in CB, 23% in URD, and 13% in RD at 3 years, respectively (P=0.0001)]. Among CB recipients in CR1, age at allo-SCT (45 years or older) was solely a significant adverse prognostic factor in multivariate analysis. Among patients younger than 45 years who received allo-SCT in CR1, OS after CB transplantation was significantly better than that after allo-SCT from mismatched URD (4-year OS: 68% vs. 49%, P=0.04). Similarly, OS was not different by donor source in subsequent CR or non-CR [Subsequent CR: 48% in CB, 39% in URD and 48% in RD, P=0.33; non-CR: 18% in CB, 21% in URD, and 15% in RD, P=0.20 at 4 years, respectively]. Conclusions: Allo-SCT using CB led to similar outcomes as either RD or URD in any disease status. CB transplantation is a good alternative for adult Ph(-) ALL patients without a suitable RD or URD.


2019 ◽  
Vol 37 (7) ◽  
pp. 580-588 ◽  
Author(s):  
Charles Craddock ◽  
Daniel Slade ◽  
Carmela De Santo ◽  
Rachel Wheat ◽  
Paul Ferguson ◽  
...  

PURPOSE Salvage options for patients who relapse after allogeneic stem-cell transplantation (allo-SCT) for acute myeloid leukemia (AML) and myelodysplasia (MDS) remain limited, and novel treatment strategies are required. Both lenalidomide (LEN) and azacitidine (AZA) possess significant antitumor activity effect in AML. Administration of LEN post-transplantation is associated with excessive rates of graft-versus-host disease (GVHD), but AZA has been shown to ameliorate GVHD in murine transplantation models. We therefore examined the tolerability and activity of combined LEN/AZA administration in post-transplantation relapse. PATIENTS AND METHODS Twenty-nine patients who had relapsed after allo-SCT for AML (n = 24) or MDS (n = 5) were treated with sequential AZA (75 mg/m2 for 7 days) followed by escalating doses of LEN on days 10 to 30. Dose allocation and maximum tolerated dose (MTD) estimation were guided by a modified Bayesian continuous reassessment method (CRM). RESULTS Sequential AZA and LEN therapy was well tolerated. The MTD of post-transplantation LEN, in combination with AZA, was determined as 25 mg daily. Three patients developed grade 2 to 4 GVHD. There was no GVHD-related mortality. Seven of 15 (47%) patients achieved a major clinical response after LEN/AZA therapy. CD8+ T cells demonstrated impaired interferon-γ/tumor necrosis factor–α production at relapse, which was not reversed during LEN/AZA administration. CONCLUSION We conclude LEN can be administered safely post-allograft in conjunction with AZA, and this combination demonstrates clinical activity in relapsed AML/MDS without reversing biologic features of T-cell exhaustion. The use of a CRM model delivered improved efficiency in MTD assessment and provided additional flexibility. Combined LEN/AZA therapy represents a novel and active salvage therapy in patients who had relapsed post-allograft.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3720-3720
Author(s):  
Sebastian Tuve ◽  
Konrad Mager ◽  
Rebekka Wehner ◽  
Felix Bahr ◽  
Uta Ölschlegel ◽  
...  

Abstract Abstract 3720 Background: Dendritic cells (DCs) are professional antigen-presenting cells which display an extraordinary capacity to induce, sustain and regulate T cell responses. Recently, 6-sulfo LacNAc+ (slan) DCs (formerly termed M-DC8+ DCs) have been described as a major subpopulation of proinflammatory human blood DCs which are principal producers of tumor necrosis factor-alpha and interleukin-12. In addition, it has been demonstrated that slanDCs efficiently induce antigen-specific CD4+ and CD8+ T cells and direct the polarization of naïve CD4+ T lymphocytes into Th1 cells. In the present study, we investigated the reconstitution kinetics of slanDCs after allogeneic stem cell transplantation (aSCT) in comparision to CD1c+ myeloid DCs and plasmacytoid DCs representing two additional major human blood DC subsets. Material and Methods: The frequency of slanDCs, CD1c+ myeloid DCs and plasmacytoid DCs in the peripheral blood was quantified by flow cytometry in 70 patients following aSCT at different time points in early engraftment (<30 days post transplantation) and late engraftment (30–100 days post transplantation). To assess the individual DC subsets we used pregating of the HLADR+Lin− subset and antibodies against the following antigens: 6-sulfo LacNAc (slanDCs), BDCA-1 (CD1c+ myeloid DCs) and BDCA-2 (plasmacytoid DCs). Maturation status was determined by analyzing the surface expression of HLADR and CD86. Results: (1) Early engraftment (<30 days post transplantation): In the early phase after transplantation CD1c+ myeloid DCs and plasmacytoid DCs show rapid engraftment. These DC subsets are predominant in early engraftment. In contrast, slanDCs only represent a minor proportion of DCs in the first month after transplantation. However, in contrast to CD1c+ myeloid DCs and plasmacytoid DCs which display an immature phenotype, the majority of slanDCs are mature in early engraftment. (2) Late engraftment (>30 days post transplantation): Interestingly, in the late phase post transplantation, the frequency of slanDCs steadily increases and these DCs represent the most abundant DC subpopulation in the second and third month post transplantation. The frequency of CD1c+ myeloid DCs and plasmacytoid DCs remains unchanged. Again, the majority of slanDCs show a mature phenotype in contrast to CD1c+ myeloid DCs and plasmacytoid DCs. Conclusion: Whereas the early engraftment phase after aSCT is dominated by CD1c+ myeloid DCs and plasmacytoid DCs, slanDCs represent the most abundant DC subset in the late engraftment phase. Furthermore, in both engraftment phases the majority of slanDCs display a mature phenotype in contrast to CD1c+ myeloid DCs and plasmacytoid DCs. Current studies are focused on functional assays and the role of individual DC populations in acute graft-versus-host disease and graft-versus-leukemia responses in the early and late phase following aSCT. Disclosures: Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.


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