Outcomes of unrelated donor stem cell transplantation with or without anti-thymocyte globulin used as graft-versus-host disease prophylaxis in patients with acute leukaemia and myelodysplastic syndrome

Author(s):  
Georgina Gener ◽  
Montserrat Batlle ◽  
Mireia Morgades ◽  
María-José Jiménez ◽  
Christelle Ferrà ◽  
...  
Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2303-2303
Author(s):  
Loic Fouillard ◽  
Myriam Labopin ◽  
Eliane Gluckman ◽  
Alois Gratwohl ◽  
Francesco Frassoni ◽  
...  

Abstract Syngeneic haematopoietic stem cell transplantation (HSCT) is a rare situation and is usually characterised by a high relapse rate because of the absence of graft versus leukaemia effect. We report results of syngeneic HSCT reported to the EBMT registry from 1975 to 2003. One hundred and 24 acute myeloid leukaemia (AML) and 104 acute lymphoblastic leukaemia (ALL) were reported comprising 150 adults and 78 children, 133 males and 95 females. The number of patients in first complete remission (CR1) was 137, comprising 93 AML (72 adults and 21 children) and 44 ALL (33 adults and 11 children). The number of patients in second complete remission (CR2) was 52 comprising 12 AML (9 adults and 3 children) and 40 ALL (11 adults and 29 children). The number of patients in more advanced disease (AD) was 39 comprising 19 AML (16 adults and 3 children) and 20 ALL (9 adults and 11 children). Total body irradiation was given to 36% of patients. Prophylaxis of graft versus host disease was given to 10% of patients. Source of stem cells was bone marrow for 81% of patients, peripheral blood for 18% and both for 1%. Outcome at 5 years showed for adult patients with AML in CR1 (n=72) a leukaemia free survival (LFS) of 56+/−7%, a relapse incidence (RI) of 37+/−7% and a non relapse mortality (NMR) of 11+/−5%. For adult patients with ALL in CR1 (n=33), LFS was 60+/−10%, RI 38+/−10% and NRM 3+/−3%. Outcome at 5 years showed for children with AML in CR1 (n=21) a LFS of 61+/−11%, a RI of 39+/−11% and a NMR of 0%. For children with ALL in CR2 (n=29), LFS was 46+/−10%, RI 52+/−10% and NRM 5+/−5%. Acute graft versus host disease (GVHD) was diagnosed in 12% of patients, 7% grade 1 and 5% grade ≥ 2. Chronic GVHD was observed in 2% of patients. These retrospective study indicates that syngeneic HSCT can lead to a high LFS in patients with acute leukaemia in CR1 and that GVHD is not a rare event. A graft versus leukemia effect is highly probable in syngeneic HSCT.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3671-3671
Author(s):  
R. Gregory Bociek ◽  
James E. Talmadge ◽  
James C. Lynch ◽  
Charles A. Enke ◽  
Charles A. Kuszynski ◽  
...  

Abstract Background/Patients and Methods: NST is increasingly being used as a means of establishing a graft-versus-malignancy (GVM) effect with less regimen related toxicity. Between 9/01 and 7/04, 39 patients (pts) with high risk/relapsed/refractory HM who were not candidates for full intensity allogeneic stem cell transplantation underwent NST using Pentostatin/TBI. The median age of pts was 52 years (range 22–70). The median number of prior therapies was 4 (range 0–8) including prior autologous stem cell transplantation in 22 pts. Diseases transplanted included chronic lymphocytic leukemia/indolent non-Hodgkin’s lymphoma (NHL, n=6), aggressive NHL (n=8), mantle cell lymphoma (n=3), Hodgkin’s disease (n=6), myeloproliferative disorders (n=4), myelodysplastic syndromes (n=4), and acute myelogenous leukemia (AML, n=8). Conditioning consisted of Pentostatin 4 mg/m2 daily on day −21, −20, and −19, followed by 200 cGy TBI on day −1. Post-grafting immunosuppression consisted of cyclosporine/mycophenolate mofetil. Results: Stem cell transplantation was from matched related (n=14) or unrelated (n=25) donors. Death prior to 100 days post transplant occurred in 7 patients. Grade III/IV toxicities included hematologic (n=10 pts), infectious (n=5) and other non-infectious (n=4). The median nadir values (day −21 to day 0) for hemoglobin, neutrophil count and platelet count were 10.7 g/dl (range 7.8–12), 1056/mm3 (range 0–5336), and 174/mm3 (range 24–523) respectively. Three pts failed to engraft; two patients with myelofibrosis (both of whom had autologous reconstitution) and one patient with high risk AML (who died of complications of fungal sepsis without hematologic recovery). The median chimerism values for CD3+ cells and WBC at day 28 are 80% and 95% donor cells respectively. The median chimerism values for CD3+ and WBC at day 70 are 95% and 95% respectively. There have been no late graft failures. The cumulative incidence of all grades of acute graft-versus-host disease at day 100 was 40% and was more common in unrelated donor transplants (60% vs. 15%, P=0.012). Chronic graft-versus-host disease has developed in 69% of patients. The cumulative incidence of relapse for all patients is 30%, and is lower for unrelated donor transplants than matched related donor transplants (46% vs. 20%, P=0.02). The probability of event-free and overall survival at two years is 52% and 56% respectively. Conclusions: This regimen is associated with acceptable toxicity. Engraftment has not been an issue with the exception of two pts with myelofibrosis. Pts receiving unrelated donor grafts have a higher incidence of graft-versus-host disease and a lower relapse rate. This represents indirect support for the presence of a GVM effect. A prospective study using a modified Pentostatin schedule (starting at day − 10) is ongoing based on the nadir of host T-cells identified in this study.


Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 717-724 ◽  
Author(s):  
William J. Jordan ◽  
Paul A. Brookes ◽  
Richard M. Szydlo ◽  
John M. Goldman ◽  
Robert I. Lechler ◽  
...  

Abstract Despite the success of human leukocyte antigen (HLA) typing in allogeneic stem cell transplantation (SCT) it is rare to find an unrelated donor that is perfectly matched, making identification of “permissive” mismatches of paramount importance. Here, we describe novel associations between donor T-cell cytokine production during donor-antipatient mixed lymphocyte reactions (MLRs) and acute graft-versus-host disease (aGVHD). The data reveal positive correlations between both Th1-type and Th2-type cytokine production and GVHD and the assay established could potentially represent a useful tool for identification of permissible unrelated SCT donors. Associations between interleukin 13 (IL-13) levels and aGVHD were by far the strongest predictor of a GVHD (P = .0002). All patients suffering severe (grade III) aGVHD following SCT had donors who produced very high pretransplantation IL-13 responses, while those developing little or no aGVHD (grades 0-I) produced no IL-13 at all. IL-13 levels were independent of all other cytokines measured as well as cytotoxic T-lymphocyte precursor (CTLp) frequencies. The cytokines IL-5, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) also predicted development of aGVHD (P < .05 for all 3), appearing to be coproduced in the assay and correlating with estimated CTLp frequencies. The data challenge the notion that aGVHD is purely a Th1-type cytokine-driven response, high-lighting a novel and highly significant link between the Th2-type cytokine IL-13 and aGVHD.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4070-4070
Author(s):  
Jun Fang ◽  
Chenghao Hu ◽  
Mei Hong ◽  
Qiuling Wu ◽  
Yong You ◽  
...  

Abstract Abstract 4070 Introduction: Enhanced risk of graft-versus-host disease (GVHD) makes one of major critical barriers to successful unrelated donor hematopoietic stem cell transplantation (URD-HSCT). Antithymocyte globulin (ATG) has been combined to standard GVHD prophylaxis regimens and significantly reduced GVHD in URD-HSCT. But ATG is associated with increases of infections and post-transplant lympholiferative disease (PTLD). Thus it is valuable to find alternative immunosuppressive agent for GVHD prophylaxis in URD-HSCT. Basiliximab and daclizumab, two anti-CD25 monoclonal antibodies, prevent graft failure in renal transplantation, which also effectively treat steroid-refractory graft-versus-host disease (GVHD). However, only few researches report that anti-CD25 monoclonal antibodies prevent GVHD. Here we firstly retrospectively explored the prophylactic effects of basiliximab or daclizumab against GVHD in 93 patients with hematological malignancies following unrelated donor peripheral blood stem cell transplantation (URD-PBSCT). Patients/methods: Between April 2004 and May 2011, 93 patients with hematological malignancies received basiliximab or daclizumab additional to standard GVHD prophylaxis regimens and underwent URD-PBSCT in our department. Their clinical data were retrospectively collected and analyzed. All patients received GVHD prophylaxis regimen consisting of cyclosporine A, short-course methotrexate, mycophenolate mofetil and an anti-CD25 monoclonal antibody. Basiliximab was administrated to 71 patients at a dose of 20 mg, while daclizumab was given to 22 patients at a dose of 1 mg/kg on day 0 (2 hours before transplantation) and day +4. Eighteen patients were 8/8 identical, 41 were 7/8 identical and 34 were 6/8 identical at HLA-A,-B,-Cw and -DRB1. The median number of infused nucleated cells and CD34+ cells were 7.5×108/kg and 5.8×106/kg, respectively. Results: i) All the recipients achieved engraftment. The median time to neutrophil recovery and platelet recovery were 12 days and 15 days, respectively. The rates of grade II-IV and III-IV acute GVHD (aGVHD) were 35.5% and 18.3%, respectively. Chronic GVHD (cGVHD) developed in 43.4% of evaluable patients. The limited cGVHD rate was 27.6% and the extensive cGVHD rate was 15.8%. The transplantation-related mortality (TRM) was 19.4% while relapse rate (RR) was 10.8%. The 2-year overall survival (2-yr OS) reached 74.2% and disease free survival (2-yr DFS) accumulated to 69.6% during a median follow-up of 24 months. ii)The side effects of basiliximab and daclizumab were moderate and tolerable. The infectious rate was 66.7% including 44.1% bacterial infection, 10.8% probable or proven invasive fungal infection, and 11.8% mixed infection. The infection-related mortality was 7.5%. The CMV reactivation rate was 46.2% and only one patient suffered CMV pneumonia. Moreover there was no clinical evidence of PTLD. iii) There were no significant differences in aGVHD onset and survival between daclizumab and basiliximab group. However, basiliximab presented superior prophylactic effects on cGVHD than daclizumab (cGVHD rate, 31.1% versus 66.7 %, P=0.007). iiii) The aGVHD rate, cGVHD rate, RR, TRM, 2-yr OS and 2-yr DFS were compared among different HLA matching groups. There were significant differences in the occurrence of grade II-IV aGVHD (11.1% versus 36.6%, P=0.047) and cGVHD(18.8% versus 51.6%, P=0.03) between HLA 8/8 identical group and HLA 7/8 identical group. Comparing HLA 8/8 identical group versus HLA 6/8 identical group, there were not only significant decreases in the rate of grade II-IV aGVHD (11.1% versus 47.1%, P=0.01) and grade III-IV aGVHD (5.6% versus 32.4%, P=0.039), but also a significant increase in the RR (22.2% versus 2.9%, P=0.043). There were no significant differences between HLA 7/8 identical group and HLA 6/8 identical group. Interestingly, the survival was not significantly different among three HLA matching groups. Conclusion: Basiliximab or daclizumab prevents GVHD efficiently and feasibly following URD-PBSCT, especially in HLA identical or only one allele mismatched recipients. Furthermore, anti-CD25 monoclonal antibodies benefit the outcome, even for those recipients with two or more HLA disparities. Basiliximab has similar effects on aGVHD prophylaxis but superior effects on cGVHD prophylaxis than daclizumab. Further prospective and randomized control studies are needed. Disclosures: Off Label Use: Drug: basiliximab (Simulect, Novartis Pharmaceuticals); daclizumab (Zenapax, Roche Pharmaceuticals). Purpose: for graft-versus-host disease prophylaxis following unrelated donor peripheral blood stem cell transplantation.


2020 ◽  
Vol 12 (1) ◽  
pp. e2020002
Author(s):  
Matteo Chinello ◽  
Rita Balter ◽  
Massimiliano De Bortoli ◽  
Virginia Vitale ◽  
Ada Zaccaron ◽  
...  

Background: Chronic graft versus host disease (cGVHD) occurs in 20-30% of paediatric patients receiving haemopoietic stem cell transplantation (HSCT). Neuromuscular disorders such as polymyositis are considered a rare and distinctive but non-diagnostic manifestation of cGVHD and, in absence of other characteristic signs and symptoms, biopsy is highly recommended to exclude other causes. Case report: We report a case of a 17-months-old child affected by hemophagocytic lymphohistiocytosis who underwent a matched unrelated donor haematopoietic stem cell transplantation (HSCT). She developed a severe cGVHD-related polymyositis that was successfully treated with high-dose steroid therapy, rituximab and sirolimus. Conclusions: This is the first case of cGVHD-related-polymyositis described in a pediatric patient which was successfully treated with rituximab.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5925-5925
Author(s):  
Meltem Kurt Yuksel ◽  
Ayla Gokmen ◽  
Muhit Ozcan ◽  
Onder Arslan ◽  
Osman Ilhan ◽  
...  

Abstract Haploidentical donors are alternative stem cell sources for the patients without matched related and unrelated donors. Finding a full match unrelated donor takes at least 6 months. Most of the patients who have advanced acute leukemia die during this period. Unfortunately, they also loose the chance of haploidentical stem cell transplantation (SCT). Aim: To report the outcome of six patients whom underwent haploidentical stem cell transplantation using FLAMSA regimen as initial reduction of leukemic burden. Patients and Treatment: There were six patients (F/M: 3/3) who admitted to transplantation unit between November 2012 and December 2013. Table 1 shows the characteristics of patients. Patients received fludarabine 30mg/m2, ARA-C 2gm/m2, Amsacrine 100 mg/m2 (FLAMSA) consequently 4 days before the intiation of conditioning protocol. According to the conditioning protocol number of the rest days changed (Table 2). For transplantation G-CSF mobilized peripheral blood stem cells were used. No graft manipulation was performed, 5x10e6 CD34+ cells/kg were requested. Graft versus host disease (GVHD) prophylaxis: Cyclophosphamide 50mg/kg/day (+3,+4), Tacrolimus 0.03 mg/kg/day +5 and MMF 3x15mg/kg +6 was started. In the absence of GVHD, MMF was discontinued by day +30, tacrolimus was tapered from day +60 to +100. Results: All of the patients had active diseases. Three of the six patients died during conditioning. Transplantation related mortality (TRM) was 50%. The other three patients were alive on the day 100. Overall survive (OS) on day 100 was %50. Two patients (22%) lived beyond 6 months. Of these two, one of them has completed the first year (16%) and is still alive without GVHD or disease relaps. Outcome of the patients are shown in Table 2. Discussion: The patient number is so restricted to draw any conclusions from this report but we know that Allogeneic SCT is the most effective treatment for a variety of hematologic malignancies. The current data suggest that the chosen sequential strategy of intensive chemotherapy followed after a few days of rest by allogeneic SCT has encourging results. Combining this modality with haploidentical transplantation may represent a step forward in the treatment of refractory hematologic malignancies. Table1: Patients’ and donors’ characteristics Patient no Gender Patient Age Diagnosis Tx no PRA Donor Donor age 1 M 37 ALL 1st Neg Brother 44 2 F 47 ALL 1st Neg Son 23 3 F 44 AML 1st Neg Son 22 4 M 41 AML 3rd(2MSD) Neg Mother 65 5 F 26 AML 2nd(1MUD) Neg Mother 54 6 F 46 ALL 2nd(1MSD) Neg Sister 53 M: Male F: Female ALL: Acute lymphoblastic leukemia, AML: Acute myeloblastic leukemia, Tx no: Number of transplantation, PRA: Panel Reactive Antibody, Neg: Negative MS:Match Sibling Donor, MUD Match Unrelated Donor) Abstract 5925 Table 2: Patients’ outcome Patient no Conditioning regimen Rest day (s) after FLAMSA Engraftment PLT 20/ NEU0.5 Chimerism on day 30 Engraftment failure Reinfusion of peripheral blood CD34+ GVHD Grade 3-4 Comorbid condition Status after SCT 1 MEL50mg/m2/day (-5,-4) TBI Gy (-3,-2,-1) -6 Yes Full Yes +105.day Yes No Exitus +210 day GVHD 2 MEL50mg/m2/day (-5,-4) TBI 4Gy(-3,-2,-1) -6 Yes Full No No No No Alive +390day 3 MEL 200mg/m2 (-1) -3,-2 No - - - - IPA Exitus+14day Gram negative septicemia 4 BU 3.2mg/kg/day (-5,-4,-3,-2) MEL 140mg/m2/day (-1) -9,-8,-7,-6 No - - - - IPA Exitus+12day Candidemi 5 MEL 200mg/m2 (-1) -3,-2 Yes Full Yes +125day No IPA Alive +240 day 6 BU 3.2mg/kg/day (-5,-4,-3,-2) MEL 140mg/m2/day (-1) -9,-8,-7,-6 No - - NA Panniculitis IPA Exitus day 0 BU: Busulfan, Mel: Melfelan, TBI: Total Body Irradiation, PLT 20: Platelet > 20.000 NEU 0.5: Neutrophil>500, GVHD: Graft versus Host Disease, IPA: Invasive Pulmonary Aspergillozis, Disclosures No relevant conflicts of interest to declare.


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