Ruxolitinib for Therapy of Graft-versus-Host Disease

Objective. Steroid-resistant graft-versus-host disease (GvHD) is a major challenge after allogeneic stem cell transplantation and associated with significant morbidity and mortality. There is no therapeutic standard defined beyond calcineurin inhibitors (CNI) and steroids. Furthermore, some patients may have contraindications against CNI or high-dose steroids. Efficacy of ruxolitinib against GvHD has been described recently. Methods. Ruxolitinib was used for treatment of acute or chronic GvHD in eight patients. The patients either needed intensification of therapy or had contraindications against use of CNI or high-dose steroids. Results. Supplementation of therapy in acute GvHD with severe diarrhea with ruxolitinib was unsuccessful. All these patients died from acute GvHD. Introduction of ruxolitinib into therapy and relapse prophylaxis in other patients was successful in 4/4 cases (CR=3, PR=1). Indications for ruxolitinib were contraindications against CNI due to aHUS in two cases and the need for steroid sparing in two other cases. None of these patients suffered from diarrhea at the initiation of ruxolitinib. Conclusion. Ruxolitinib was effective for therapy of acute and chronic GvHD in higher lines in patients without severe diarrhea. Ruxolitinib could replace successfully CNI and high-dose steroids. Further investigations are necessary to define the position of ruxolitinib in GvHD-therapy.

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Mesenchymal Stem Cells for Treatment of Refractory Chronic Graft-Versus-Host Disease.

Blood ◽

10.1182/blood.v110.11.4968.4968 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4968-4968

Author(s):

Weng Jianyu ◽

Xin Du ◽

Xiang Peng ◽

Zhang Xiumin ◽

Suijin Wu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Immunosuppressive Agents ◽

Steroid Resistant ◽

Host Disease ◽

Graft Versus Host

Abstract Refractory extensive chronic graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation (SCT) is associated with high mortality [Margolis J., SeminOncol 2000].However, conventional therapies including steroids are often unsuccessful in those patients with multiorgan involvement and are associated with significant therapy-related complications and poorly life quality. Mesenchymal stem cells (MSCs) have immunomodulatory effects [Tse WT et al., Transplantation 2003; Spees JI et al.,Proc Natl Acad Sci USA 2003]. Recently MSCs have been given intravenously to treat seven steroid resistant acute GVHD patients and one patient with chronic GVHD. MSCs effects in chronic GVHD is rarely known, although this successfully experience suggests that MSCs have been well tolerated and had a powerful immunosuppressive effects on acute GVHD. [Katarina Le Blanc et al., Lancet 2004; Olle Ringden., Transplantation 2006 ]. Here, we present our experience of using MSCs for treatment of Thirteen patients with refractory chronic GVHD. Between May 2005 and March 2007, thirteen patients (8 male, 5female) with hematological malignancies with a median age of 26(range:15 to 40) years who had received peripheral stem cells from sibling donors. All patients developed steroid resistant or extensive chronic GVHD, with progressive involvement of the skin(13), liver(10), oral mucosa(12),ocular glands(12), and thrombocytopenia (1) when the immunosuppressive agents were taped after five to twenty-four months. The MSC dose was median 1.0 ×106 cells/kg body weight of the recipient. In all, thirteen patients had at least received one dose, seven patients received more than two doses. MSC donors were in seven cases HLA-identical siblings, six unrelated mismatched donors. No side-effects were seen after MSCs infusions. All patients have responded after follow-up of the median time 15 months. One patient with moderate cGVHD had a complete responses, and discontinued all of the immunosuppressive agents without relapse more than 18.4 months after MSC infusion. Three moderate and two patients with severe chronic GVHD improved to mild degree, and six severe turned to moderate degree. Complete resolution was seen in gut(2/3), liver(5/10), skin(5/13), oral(6/12) and eye(2/12). One patient responded in skin, liver, oral mucose and eye, but developed in lung (bronchiolitis obliterans, BO) score of 2 which are considered severe chronic GVHD. Mean follow-up periods was 27m (rang: 14 to48m), Leukemia free survival(LFS)rate were 85%(11/13), and the overall survival (OS)rate were 92.3%(12/13). Our experience suggests that MSC infusion is a safe and effective adjunct therapy for refractory extensive chronic GVHD with resistance to conventional therapy. But more prospective, controlled studies with MSCs for treatment of GVHD should be performanced to evaluate this new treatment exactly.

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Reduction in the Incidence and Severity of Graft Versus Host Disease in HLA-Matched and Haploidentical Bone Marrow Transplantation Using Posttrasplant Cyclophosphamide. Experience of Two Latino-American Institutions

Blood ◽

10.1182/blood.v124.21.5880.5880 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5880-5880

Author(s):

Roberto Ovilla ◽

Uendy Perez-Lozano ◽

Dannia Calles-Payan ◽

Lucia A Reynolds-Ocampo ◽

Gabriela Ruiz-Reyes ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Graft Versus Host Disease ◽

Graft Rejection ◽

Marrow Transplantation ◽

Acute Gvhd ◽

Chronic Gvhd ◽

High Dose ◽

Host Disease ◽

Graft Versus Host

Abstract The Graft Versus Host Disease (GVHD) grades II-IV is present in up to 40% in Human Leucocyte Antigen (HLA) - identical related transplants and up to 80% of non-related. The HLA-haploidentical bone marrow transplantation (BMT) has been associated with significant risks of graft rejection and severe GVHD, as an excessive alloreactivity by host and donor T cells. High dose of Cyclofosfamide (Cy) after BMT inhibits both graft rejection and GVHD. We want to share our experience in preventing GVHD in HLA - haploidentical alloBMT and HLA-matched related BMT using the strategy of Cy post-Transplant. We evaluated 25 patients from March 2013 to June 2014, all of them were in advanced stages of the disease or they have characteristics of poor prognosis before transplantation. All patients received non-myeloablative conditioning and Cyclofosfamide (Cy) 50 mg/Kg postrasplant (on days 3 and 4 after transplantation), Mycophenolate mofetil (from day 5 to 35) and Tacrolimus (from day 5 to 180). The 64% (16) were male, mean age 30.6 years (range 2 – 67 years), with a average follow-up of 198 days (range 14-512 days). The 76% (19) were HLA-matched related alloBMT (7 patients) and HLA-haploidentical alloBMT (12 patients) in hematological malignancies, the rest of trasplants (24%) were HLA-haploidentical alloBMT in benign hematological diseases, overall survival (OS) at day 180 by type of transplant was 70%, 64%, and 67% respectively. 28% (7) had graft failure. 11 patients had no acute GVHD, 10 patients had GVHD grade I-II, and 3 patients had grade III, only 1 patient died because of grade IV (P = 0.005). Chronic GVHD occurred in 4 patients (16%). As a complication related to Cy therapy, hemorrhagic cystitis was observed 32%(8). Posttransplantation cyclophosphamide is able to reduce the likelihood of developing chronic GVHD and reduces the severity of acute GVHD, it plays an important role in the feasibility of a haploidentical transplant because the lower incidence of GVHD. Our results showed one of the most satisfactory and encouraging studies on the use of post-transplantation Cy performed in Latin America. Disclosures No relevant conflicts of interest to declare.

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Immune Mediated Cerebellar Ataxia: An Unknown Manifestation of Graft-versus-Host Disease

Acta Haematologica ◽

10.1159/000494423 ◽

2018 ◽

Vol 141 (1) ◽

pp. 19-22

Author(s):

Liat Shargian-Alon ◽

Pia Raanani ◽

Uri Rozovski ◽

Tali Siegal ◽

Shlomit Yust-Katz ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Graft Versus Host Disease ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Cerebellar Atrophy ◽

Acid Decarboxylase ◽

High Dose ◽

Host Disease ◽

Graft Versus Host ◽

Aged Woman

Neurologic complications of allogeneic hematopoietic cell transplantation (allo-HCT) include infections, cerebrovascular events, therapy-induced neurotoxicity, recurrent malignancies, and neurologic manifestations of graft-versus-host disease (GVHD). Anti-glutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is a well-established disorder of autoimmune origin, but there are no reports in the literature of its occurrence following allo-HCT. We describe a middle-aged woman with chronic GVHD after allo-HCT who presented with a rapidly progressive cerebellar syndrome. Thorough investigation revealed only cerebellar atrophy on brain imaging and positive anti-GAD65 antibodies in serum and cerebrospinal fluid suggesting the diagnosis of anti-GAD antibody-associated cerebellar ataxia. Despite prompt treatment with high-dose corticosteroids, intravenous immunoglobulins, and rituximab, the patient’s condition rapidly deteriorated, and she died 4 months later. This case suggests that anti-GAD antibody-associated cerebellar ataxia may be a rare manifestation of chronic GVHD.

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Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽

10.46765/2675-374x.2020v1n1p53-66 ◽

2020 ◽

Vol 1 (1) ◽

pp. 53-66

Author(s):

Vaneuza A. M. Funke ◽

Maria Claudia Rodrigues Moreira ◽

Afonso Celso Vigorito

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Cell Transplant ◽

Primary Therapy ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, involving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

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The role of antigen-presenting cells in triggering graft-versus-host disease and graft-versus-leukemia

Blood ◽

10.1182/blood-2006-12-022038 ◽

2007 ◽

Vol 110 (1) ◽

pp. 9-17 ◽

Cited By ~ 108

Author(s):

Ronjon Chakraverty ◽

Megan Sykes

Keyword(s):

Graft Versus Host Disease ◽

Acute Gvhd ◽

Tissue Injury ◽

Chronic Gvhd ◽

Host Disease ◽

Graft Versus Host ◽

Graft Versus Leukemia ◽

Donor T Cells ◽

Antigen Presenting

After allogeneic blood or bone marrow transplantation, donor T cells interact with a distorted antigen-presenting cell (APC) environment in which some, but not all, host APCs are replaced by APCs from the donor. Significantly, host APCs are required for the priming of acute graft-versus-host disease (GVHD). Donor APCs play a lesser role in the induction of acute GVHD despite their predicted capacity to cross-present host antigens. In contrast, donor APCs may play a role in perpetuating the tissue injury observed in chronic GVHD. Host APCs are also required for maximal graft-versus-leukemia responses. Recent studies have suggested potential strategies by which the continued presence of host APCs can be exploited to prime strong donor immunity to tumors without the induction of GVHD.

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Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia [published erratum appears in Blood 1989 Aug 15;74(3):1180]

Blood ◽

10.1182/blood.v73.6.1720.1720 ◽

1989 ◽

Vol 73 (6) ◽

pp. 1720-1728 ◽

Cited By ~ 430

Author(s):

KM Sullivan ◽

PL Weiden ◽

R Storb ◽

RP Witherspoon ◽

A Fefer ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Marrow Transplantation ◽

Acute Gvhd ◽

Blast Crisis ◽

Chronic Gvhd ◽

Chronic Phase ◽

Lymphocytic Leukemia ◽

Myelogenous Leukemia ◽

Host Disease ◽

Graft Versus Host

Abstract To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA- identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.

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Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease

Blood ◽

10.1182/blood.v84.4.1342.1342 ◽

1994 ◽

Vol 84 (4) ◽

pp. 1342-1348 ◽

Cited By ~ 106

Author(s):

JH Antin ◽

HJ Weinstein ◽

EC Guinan ◽

P McCarthy ◽

BE Bierer ◽

...

Keyword(s):

Receptor Antagonist ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Mononuclear Cells ◽

Interleukin 1 ◽

Response To Therapy ◽

Mrna Levels ◽

Steroid Resistant ◽

Host Disease ◽

Graft Versus Host

Abstract Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL- 1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.

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Graft Versus Host Disease Prophylaxis with Everolimus and Tacrolimus in Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukaemia (AML) Receiving Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT).

Blood ◽

10.1182/blood.v108.11.2886.2886 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2886-2886 ◽

Cited By ~ 1

Author(s):

Uwe Platzbecker ◽

Caroline Pabst ◽

Alexander Kiani ◽

Johannes Schetelig ◽

Martin Wermke ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Peripheral Blood ◽

Acute Gvhd ◽

De Novo ◽

Chronic Gvhd ◽

Clinical Signs ◽

Unrelated Donor ◽

Peripheral Blood Stem Cells ◽

Host Disease ◽

Graft Versus Host

Abstract Introduction: The use of a calcineurin-inhibitor in combination with methotrexate is the current standard in the prophylaxis of graft versus host disease (GVHD). Everolimus is a newly developed m-TOR inhibitor, which, besides a potent immunosuppressive action including the stimulation of regulatory CD4+foxp3+ T-cells (Tregs), seems to mediate anti-neoplastic effects in MDS and AML. Methods: We report results of a prospective study investigating for the first time a combination of everolimus (days 0–56) with tacrolimus (starting day 0) in 16 patients with MDS (RCMD n=3, RAEB-1 n=3, RAEB-2 n=3, CMMOL-1 n=1, CMMOL-2 n=1, MDS/AML n=1) or de novo AML (n=4) undergoing allogeneic myeloablative conditioning (busulfan 16 mg/kg over 4 days, fludarabine 120 mg/m² over 4 days) followed by a median of 7.0 x 106/kg CD34+ peripheral blood stem cells (PBSC) from related (n=2) or unrelated donors (n=14). It is of note that 5 unrelated donor/recipient pairs displayed one allel-mismatch whereas all others were matched in 10 out 10 HLA characters. The median age of the patients was 61 years (range 47–69) and the majority (n=7) of MDS patients were classified INT-2 or HIGH according to IPSS. Results: All patients engrafted a median of 14 days (platelets) and 17 days (neutrophils) after transplant. On day 21 and 56 after PBSCT the median number of CD4+foxp3+ cells in the blood was not significantly different from normal donors (patients, n=5: 3.2 and 2.3 x 104/ul, controls n=4: 3.7 x 104/ul) Nevertheless, the rate of acute GVHD was moderate with five patients (31 %) developing acute GVHD grade II and only one patient experiencing grade IV GVHD after cessation of immunosuppression due to thrombotic-thrombocytopenic purpura (TTP). Decrease of thrombocytes together clinical signs of TTP were seen in two additional patients while four patients developed VOD of the liver, which was fatal in one case. Extensive chronic GVHD was seen in 50 % of evaluable patients. Mucositis CTC grade III was observed in 5 patients only. The total day 100 mortality rate was 19 % and currently eleven out of sixteen patients (69%) are alive and in remission. Conclusion: Everolimus and tacrolimus are highly efficient in preventing GVHD after unrelated PBSCT in older patients with MDS and AML, which seems not to be mediated by an increase in Tregs. Nevertheless, side effects associated with thrombotic microangiopathy might be more prevalent compared to other regimens.

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Serious Acute or Chronic Graft-Versus-Host Disease after Hematopoietic Cell Transplantation: A Comparison of Myeloablative and Non-Myeloablative Conditioning Regimens.

Blood ◽

10.1182/blood.v108.11.755.755 ◽

2006 ◽

Vol 108 (11) ◽

pp. 755-755

Author(s):

Olga Sala-Torra ◽

Paul J. Martin ◽

Barry Storer ◽

Mohamed Sorror ◽

Rainer F. Storb ◽

...

Keyword(s):

Cell Transplantation ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Univariate Analysis ◽

Hematopoietic Cell ◽

Host Disease ◽

Graft Versus Host ◽

Co Morbidity

Abstract We have previously described serious graft-versus-host disease (GVHD) as a highly undesirable outcome after allogeneic hematopoietic cell transplantation (HCT). Serious GVHD encompasses death, lengthy hospitalization, major disability, or recurrent major infections related to either acute or chronic GVHD. In a previous study, we found a 25% incidence of serious GVHD among 171 consecutive patients who had HCT after non-myeloablative (NMA) conditioning between January 1998 and May 2002. To put this observation into perspective, we applied the same criteria for serious GVHD in a cohort of 264 consecutive patients who had HCT after myeloablative (MA) conditioning during the same period of time and compared results with those of the previous study. The overall incidence of serious GVHD was 17% (44/264) in the MA group, compared to 25% (43/171) in the NMA group. There were no statistically significant differences in the incidence of grades III–IV GVHD, extensive chronic GVHD or nonrelapse mortality between the two groups (Table). Patients in the NMA group were older and had higher comorbidity scores than those in the MA group. In the univariate analysis, the hazard ratio (HR) of serious GVHD for the NMA group compared to the MA group was 1.71 (95% C.I., 1.1–2.6) (p = 0.01). After adjusting for patient age, patient and donor gender, donor type, HLA-mismatch, aggressive versus indolent malignancy at HCT, remission versus relapse at HCT, myeloid versus non–myeloid malignancy, HCT co–morbidity index, and prior donor lymphocyte infusion, the HR of serious GVHD was 1.50 (95% C.I., 0.8–2.7) (p = 0.17). After censoring for recurrent or progressive malignancy after HCT, the cumulative incidence of serious GVHD at 3 years was 21% for the NMA group and 14% for the MA group, and the HR was 1.33 (95% C.I., 0.7–2.6) (p = 0.40). Reasons for categorization of GVHD as serious (i.e., death, lengthy hospitalization, major disability, or recurrent major infections) were similar between the MA and NMA cohorts. Among the 44 patients with serious GVHD in the MA group, 19 (43%) had serious acute GVHD, and 25 (57%) had serious chronic GVHD. Among the 43 patients with serious GVHD in the NMA group, 20 (46%) had serious acute GVHD, and 30 (70%) had serious chronic GVHD. Among the 264 MA patients, 28 (11%) had grade III–IV acute GVHD and 147 (56%) had extensive chronic GVHD that did not meet the criteria for serious GVHD, compared to 7 (4%) and 84 (49%) of the 171 NMA patients, respectively. We conclude that the type of pretransplant conditioning regimen does not have a large effect on the incidence of serious GVHD after HCT. Assessment of serious GVHD provides additional useful information to acute GVHD grades and the classification of limited and extensive chronic GVHD in describing overall GVHD-related outcomes after HCT. MA NMA Outcome, n (%) n = 264 n = 171 Serious GVHD 44 (17) 43 (25) Grades III–IV acute GVHD 54 (20) 27 (16) Extensive chronic GVHD 174 (66) 114 (68) 2-year nonrelapse mortality 66 (25) 43 (25)

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Mesenchymal Stem Cells for Treatment of Severe Acute Graft-Versus-Host Disease.

Blood ◽

10.1182/blood.v108.11.5304.5304 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5304-5304 ◽

Cited By ~ 6

Author(s):

Katarina Le Blanc ◽

Francesco Frassoni ◽

Lynne Ball ◽

Edoardo Lanino ◽

Berit Sundberg ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Third Party ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

Abstract Mesenchymal stem cells (MSC) from adult bone marrow have the capacity to differentiate into several mesenchymal tissues and inhibit T-cell alloreactivity in vitro. Within the EBMT MSC expansion consortium we have used MSC to treat grades III–IV acute graft-versus-host disease (GvHD) in 40 patients. The MSC dose was median 1.0 (range 0.4–9) 10^6 cells/kg body weight of the recipient. No side-effects were seen after MSC infusions. Nineteen patients received one dose, 19 patients received two doses, two patients received three and five doses respectively. MSC donors were in five cases HLA-identical sibling donors, 19 haploidentical donors and 41 third-party HLA-mismatched donors. Among the 40 patients treated for severe acute GvHD, 19 had complete responses, nine showed improvement, seven patients did not respond, four had stable disease and one patient was not evaluated due to short follow-up. Twenty-one patients are alive between six weeks up to 3.5 years after transplantation. Nine of these patients have extensive chronic GvHD. One patient with ALL has recurrent leukaemia and one patient has denovo AML of recipient origin. We conclude that MSC have immunomodulatory and tissue repairing effects and should be further explored as treatment of severe acute GvHD in prospective randomized trials.

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