Center for Allogeneic Stem Cell Transplantation

Stockholm, Sweden

Center for Allogeneic Stem Cell Transplantation

Stockholm, Sweden
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Pasquini M.C.,Medical College of Wisconsin | Zhang M.-J.,Medical College of Wisconsin | Medeiros B.C.,Stanford University | Armand P.,Dana-Farber Cancer Institute | And 43 more authors.
Biology of Blood and Marrow Transplantation | Year: 2016

The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P <.01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P =90), and worse survival (hazard ratio, 1.67; P <.01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P <.01), higher TRM (hazard ratio, 1.80; P <.01), and worse survival (HR, 2.02; P <.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P <.01) and MDS (hazard ratio, 1.79; P <.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed. © 2016 American Society for Blood and Marrow Transplantation.


Remberger M.,Center for Allogeneic Stem Cell Transplantation | Ringden O.,Center for Allogeneic Stem Cell Transplantation | Sundin M.,Karolinska University Hospital | Sundin M.,Karolinska Institutet | And 2 more authors.
Transfusion | Year: 2015

BACKGROUND In approximately two-thirds of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) no suitable related donor can be identified but an unrelated HLA-matched donor can be found through international donor registries. HSCT grafts from unrelated donors are commonly collected at distant sites. Therefore, graft storage and transportation becomes crucial in the HSCT process. We aimed to study the impact of graft quality on clinical outcome and identify factors affecting graft quality. STUDY DESIGN AND METHODS We investigated the influence of graft quality on the clinical outcome in 144 HSCT patients. Graft quality was assessed by determining the viability (7-aminoactinomycin D [7AAD]) on a frozen-thawed sample from the peripheral blood stem cell (PBSC) graft. RESULTS Patients receiving PBSCs with inferior quality (i.e., viability < 64% in the frozen-thawed sample) more frequently developed acute graft-versus-host disease (aGVHD) Grades I to IV than patients receiving grafts with better quality (p = 0.025). The transplant-related mortality (TRM) was higher in the group receiving grafts with lower viability (p = 0.03). The viability of the frozen-thawed samples was highly variable (median, 64%; range, 24%-96%). No correlation could be observed when comparing the viability in newly arrived PBSC grafts to frozen-thawed vials. Grafts with white blood cell (WBC) count of more than 300 × 109/L had lower viability than those with lower WBC counts (p < 0.001). CONCLUSION Graft quality affects clinical outcome. Patients receiving grafts with inferior quality had more aGVHD and higher TRM. There is a need for better analyses for assessing graft quality in routine HSCT care; analysis using 7AAD on fresh PBSC grafts is not sufficient. © 2015 AABB.


Olsson R.F.,Karolinska Institutet | Olsson R.F.,Uppsala University | Logan B.R.,Medical College of Wisconsin | Chaudhury S.,Ann and Robert H Lurie Childrens Hospital of Chicago | And 13 more authors.
Leukemia | Year: 2015

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 10 8 per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells. © 2015 Macmillan Publishers Limited All rights reserved.


Veys P.A.,Great Ormond Street Hospital for Children NHS Trust | Nanduri V.,Watford General Hospital | Baker K.S.,Fred Hutchinson Cancer Research Center | He W.,Medical College of Wisconsin | And 22 more authors.
British Journal of Haematology | Year: 2015

Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, P = 0·02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain. © 2015 John Wiley & Sons Ltd.


Karlsson H.,Center for Allogeneic Stem Cell Transplantation | Erkers T.,Center for Allogeneic Stem Cell Transplantation | Nava S.,Center for Allogeneic Stem Cell Transplantation | Ruhm S.,Center for Allogeneic Stem Cell Transplantation | And 2 more authors.
Clinical and Experimental Immunology | Year: 2012

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used to treat steroid-refractory acute graft-versus-host disease (GVHD) in stem cell transplant patients. Cells with similar capacities can also be found in term placental tissue. We have isolated stromal cells from term fetal membrane (FMSCs), umbilical cords (UCSCs) and placental villi (PVSCs) as well as from bone marrow and compared their immunoregulatory capacity in allogeneic settings. We found that FMSCs and UCSCs suppressed proliferation significantly in mixed lymphocyte reactions (MLRs), whereas PVSCs showed inconsistent suppressive effects. When added to MLR cultures, FMSCs suppressed the production of interferon (IFN)-γ and interleukin (IL)-17, whereas UCSCs and PVSCs promoted the production of IL-17 instead. Secretion of IL-10 was increased after addition of FMSCs and UCSCs. In this setting, BM-MSCs had no significant effect on secretion of IFN-γ, IL-17 or IL-10 in MLR cultures. When analysing the expression of adhesion markers, we noted that FMSCs expressed the highest levels of CD29 (β1), CD49d (α4) and CD54 (ICAM-1) compared to the other types of stromal cells. Thus, our data indicate that stromal cells isolated from term fetal membrane have great immunosuppressive capacity in terms of proliferation and production of proinflammatory cytokines from alloreactive T cells, and also promote anti-inflammatory IL-10. They express high levels of integrins that may be of importance in homing to inflamed tissues. Fetal membrane may provide a valuable source of cells with immunosuppressive properties and could possibly be used for treatment of acute GVHD and other inflammatory disorders. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.


Ringden O.,Center for Allogeneic Stem Cell Transplantation | Erkers T.,Center for Allogeneic Stem Cell Transplantation | Nava S.,Center for Allogeneic Stem Cell Transplantation | Uzunel M.,Center for Allogeneic Stem Cell Transplantation | And 5 more authors.
Stem Cells | Year: 2013

The placenta protects the fetus from the mother's immune system. We have previously found that fetal membrane cells (FMCs) isolated from term placenta prevent alloreactivity in vitro. FMCs share many features with bone marrow- derived mesenchymal stromal cells (MSCs), which we previously introduced to treat severe acute graft-versushost disease (GVHD). Here, we tested FMCs for treatment of steroid-refractory acute GVHD. After two passages in culture, approximately 109 FMCs were obtained from one single placenta, although not all cells from passage 0 and passage 1 were used for expansion. The FMCs were positive for CD29, CD44, CD73, CD90, CD105, and CD49d but were negative for hematopoietic, endothelial, and epithelial markers. Microsatellite polymorphism analysis showed that FMCs were of maternal origin. All FMCs used showed normal karyotype. Nine patients who had undergone hematopoietic stem cell transplantation (HSCT) and who had developed steroid-refractory grade III-IV acute GVHD were given 0.9-2.8 × 106 FMCs per kg at 15 infusions. Median age was 57 years. There was no toxicity from infusion of FMCs in eight patients. One patient had seizures after infusion. Two of eight evaluable patients had a complete response and four had a partial response, giving an overall response rate of 75%. Two patients showed no response at all. Three patients are alive from 6 to 21 months after HSCT. One patient is well and two have chronic GVHD. Thus, FMCs may be successfully used for immune modulation and tissue repair. © AlphaMed Press.


Inamoto Y.,National Cancer Center Hospital | Flowers M.E.D.,Fred Hutchinson Cancer Research Center | Wang T.,Medical College of Wisconsin | Urbano-Ispizua A.,University of Barcelona | And 27 more authors.
Biology of Blood and Marrow Transplantation | Year: 2015

Combinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia. © 2015 American Society for Blood and Marrow Transplantation.

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