Donor Lymphocyte Infusions and Second Transplantation as Salvage Treatment for Relapsed Myelofibrosis After Reduced-Intensity allografting.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1300-1300
Author(s):  
Nicolaus Kröger ◽  
Evgeny Klyuchnikov ◽  
Daniel Wolff ◽  
Martin Bornhäuser ◽  
Guido Kobbe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Complete Loss ◽  
Donor Lymphocyte Infusions

Abstract Abstract 1300 Introduction: Around 20–30% patients (pts) with primary myelofibrosis (PMF) experience relapses within 3 years after dose-reduced conditioning followed by allogeneic stem cell transplantation (HSCT). The prognosis for those pts is unclear, and standard treatment recommendations have not yet been proposed. Early withdrawal of post-transplant immunosuppression, use of dose escalating donor lymphocyte infusions (DLIs), and/or 2nd HSCT have been suggested as therapeutic options for pts relapsing after HSCT. Although DLIs were found to be effective in certain disease as salvage approach, the role of 2nd HSCT for non-responding patients remains controversial. Here we report on our multicenter experience on the use of a two-stage salvage strategy including DLIs and a 2nd RIC-HSCT in pts with post-transplant relapse of PMF. It was planned to start salvage therapy with DLI and only non-responding patients as well as patients with transformation to blast crisis and complete loss of donor chimerisms were assigned to receive a second allogeneic stem cell transplantation. Responses were evaluated using the International Working Group consensus criteria for treatment response in myelofibrosis. Additionally, the JAK2V617F mutation level (in 1 case, the MPLW515mut level) and donor chimerism were used to assess the molecular remission status. Patients/Methods: Thirty pts with morphologic (n=24) or molecular (n=6) relapse of PMF after 1st HSCT were proceeded to a salvage strategy, including DLIs and/or 2nd RIC-HSCT. Median time from transplantation to relapse was 9 months (range, 2–62). 26 pts received a median of 3 (range, 1–5) DLIs. The initial median dose was 1.2×106 (range, 0.3×104 – 8×107) consequently being increased up to 4×107 CD3+ cells/kg (range, 1×107 – 1.3×108). As a second stage, 13 non-responding pts as well as those who received no DLIs (transformation to blast phase, n=1; complete loss of donor chimerism, n=3) underwent a 2nd RIC-HSCT. The median interval between 1st and 2nd HSCTs was 17 months (range, 11–77). The majority of the patients received a reduced busulfan/fludarabine conditioning regimen for the 1st HSCT. Conditioning regimen at the 2nd RIC-HSCT for most pts (12/17, 71%) consisted of a combination of treosulfan (30-36 g/m2) with fludarabine (150-180 mg/m2), and anti-thymocyte globuline (Thymoglobulin®, 2.5–8 mg/kg). The majority of pts (15/17, 82%) received 2nd allografts from alternative unrelated (HLA-matched, n=8; mismatched, n=5), related (matched, n=1), and haploidentical donors (n=1). Results: After DLIs, responses were observed in 10/26 pts (39%; complete remission (CR): n=8; CRu (unconfirmed: no bone marrow histology: n=2). All pts maintain the response during a median follow-up of 31 months (range, 13–45). Acute (grade II-IV) and chronic GvHD occurred in 3/26 (12%) and 7/25 (28%) pts, respectively There were no cases of non-relapsed mortality (NRM), while 3/26 pts expired from progression. Seventeen pts received a 2nd RIC-HSCT and engraftment was documented in 16/17 pts (leukocytes: median, d +14; platelets: median, d +18). Responses were observed in 12/15 evaluable pts (80%; CR, n=8; CRu, n=1; partial remission (PR), n=3). Acute (II-IV) and chronic GvHD were observed in 8/17 (47%) and 6/14 pts (43%), respectively. The 1-year cumulative incidence of NRM was 6% (95% CI: 0%-18%). The cumulative incidence of relapse at 1 year was 24% (95% CI: 0%-50%). Overall for whole study population, after a median follow-up of 27 mo (range, 9 – 61), the 2-year probabilities of OS and PFS was 80% (95% CI: 62% - 98%) and 72% (95% CI: 52% - 92%), respectively. Conclusions: DLIs and/or 2nd HSCT are effective and well tolerated salvage approaches, which resulted in the majority of patients in long-term freedom from disease. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation with Reduced-Intensity, Fludarabine-Based Conditioning in Relapsed and Refractory Hodgkin’s Disease: Low Transplant-Related Mortality and Impact of Intensity of Conditioning Regimen on Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2135-2135
Author(s):  
Paolo Anderlini ◽  
Rima Saliba ◽  
Michele Donato ◽  
Sergio Giralt ◽  
Borje Andersson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Hodgkin’S Disease ◽  
Conditioning Regimen ◽  
Related Mortality

Abstract Forty patients with relapsed or refractory Hodgkin’s disease (HD) underwent allogeneic stem cell transplantation (allo-SCT) following a fludarabine-based conditioning regimen from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). The median number of chemotherapy regimens received prior to allo-SCT was five (range 2-9). Thirty (75%) and thirty (75%) patients had received prior radiotherapy or a prior autologous SCT, respectively. The median time to progression after autologous SCT was nine months (3–52). Disease status at SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens employed were fludarabine (25 mg/m sq IV x 5 days)-cyclophosphamide (1 g/m sq IV x 3 days) ± antithymocyte globulin (30 mg/kg IV x 3 days) (FC±ATG) (n=14), a less intensive regimen, and fludarabine (25 mg/m sq IV x 5 days) -melphalan (70 mg/m sq IV x 2 days) (FM) (n=26), a more intensive one. The two groups had similar demographics and prognostic factors. Chimerism studies indicated 100% donor-derived engraftment in 26/26 (100%) FM patients and in 9/13 (69%) evaluable FC±ATG patients. Day 100 and cumulative (18-month) transplant-related mortality (TRM) were 5 % and 22%, respectively for the whole group. There was a nonsignificant trend towards a lower cumulative TRM in the FM group (18% vs. 30% at 18 months, p=0.2). The cumulative incidence of acute (grade II-IV) GVHD was 38%. The cumulative incidence of chronic GVHD at 18 months was 69%. There was a trend for a lower relapse rate after the occurrence of GVHD, however, this was not statistically significant (hazard ratio 0.8; p= 0.6). Progression rates were similar in the FM and FC patients (53% vs. 57% respectively at 18 months, p=0.4). However, disease progression occurred later in FM patients (range 2–34 months) than in FC patients (range 0.7–13 months). In addition, with comparable follow-up time after progression, the FM group experienced a lower death rate after progression. Twenty-four patients (60%) are alive (fourteen in complete remission) with a median follow-up of 13 months (4–78). Sixteen patients expired (TRM n=8, disease progression n=8). FM patients had significantly better overall survival (73% vs. 39% at 18 months; p=0.03), and a trend towards better progression-free survival (37% vs. 21% at 18 months; p=0.2). We conclude that allo-SCT with fludarabine-based, less intensive conditioning from matched related and unrelated donors are feasible in high-risk HD patients with a low TRM. The intensity of the preparative regimen affects survival.

Allogeneic Stem Cell Transplantation in Multiple Myeloma: One Center Experience of 86 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3033-3033
Author(s):  
Liisa Volin ◽  
Heli Uotinen ◽  
Eeva Juvonen ◽  
Anne Nihtinen ◽  
Tapani Ruutu
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Related Mortality ◽  
Time Point

Abstract The role of allogeneic stem cell transplantation (SCT) in the treatment of multiple myeloma (MM) is unclear. High transplant-related mortality has been regarded as a particular problem. At the Helsinki University Central Hospital 86 patients with MM have been treated with allogeneic SCT since 1995. The conditioning was at first myeloablative (MA). Since 1999 reduced intensity conditioning (RIC) after autologous SCT has been used in most cases, but a number of young patients with aggressive disease have been transplanted with MA conditioning. Of the patients 42 were male and 44 female. The median age at SCT was 50 (27–64) years. The median number of chemotherapy lines before allogeneic SCT was 1 (range 1–7). Prior autologous SCT had been performed to 55 patients. The median time from diagnosis to allogeneic SCT was 12 (4–168) months, and the time between autologous and allogeneic SCT 6 (2–146) months. At the time of allogeneic SCT 9 patients were in CR, 63 in PR, 4 had stable disease, and 10 progressive disease. 72 patients had a sibling donor: 68 were HLA-identical, one 1 antigen mismatch, 3 identical twins. 14 patients had an HLA-matched unrelated donor. The conditioning was MA in 32 and RIC in 54 patients. The MA conditioning consisted of Cy/TBI in 22, Mel/TBI in 3, and Treosulfan/Fld in 7 patients. RIC was the Seattle protocol (Fld/TBI 2 Gy) in 45, reduced Treosulfan/Fld in 8, and Fld/Cy in 1 patient. 26 patients received a BM graft and 60 patients a PB graft. As GVHD prophylaxis, 18 patients were given CsA/Mtx, 20 CsA/Mtx/MP, 45 CsA/MMF, and 3 nothing (identical twins). The median follow-up time from allogeneic SCT was 39 (2–136) months, 46 (7–136) months for the MA patients and 34 (2–92) months for the RIC patients, respectively. The OS was 50% at 61 months post SCT and there have been no deaths after this time-point. The median PFS was 31 months. After this time-point the disease has progressed in one case, at 90 months. Of the 32 MA patients 16 (50%) and of the 54 RIC patients 22 (41%) have achieved CR after SCT. The cumulative incidence of acute GVHD grade II-IV was 28%. The cumulative incidence of chronic GVHD was 72%, 58% in the MA and 83% in the RIC patients (p=0.074). The incidence of extensive chronic GVHD was significantly (p=0.012) higher in RIC than MA patients, 66% vs. 23%. There were no statistical differences in the incidence of acute or chronic GVHD by donor type (72 siblings/14 unrelated). The cumulative 100-day transplant related mortality was 4.5% and that of the whole follow-up time 14%. 26 patients have died. The cause of death was myeloma in 15, GVHD in 7, and infection in 4 patients. In conclusion, in the present material transplant-related mortality was low and the survival encouraging, supporting the use of allogeneic transplantation with curative aim in selected cases. Developing chemotherapy, given prior to transplantation, may improve the results.

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

Effect of Rituximab on the Incidence of GVHD in Lymphoma Patients who Received the BEAM-Conditioning and an Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4980-4980
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Daniel R. Couriel ◽  
Grace-Julia Okoroji ◽  
Sandra Acholonu ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
Study Group

Abstract It has been postulated that B cells functioning as antigen-presenting cells may have an important role in the pathogenesis of GVHD. Depletion of donor cells from B-cells resulted in a low incidence of GVHD in mouse model (Schultz et al. BMT1995:16:289–289). More recently, we observed a lower incidence of chronic (and to a lesser extent acute GVHD) in patients with CLL who received an allogeneic stem cell transplantation after a non-myeloablative conditioning regimen containing rituximab (Exp Hematol32:28–35, 2004). The purpose of this study is to investigate the effect of rituximab on GVHD in the setting of a more intense chemotherapy with BEAM, in patients who received an allogeneic peripheral blood stem cell from HLA-identical siblings. To test this hypothesis, we retrospectively studied 11 consecutive patients with non-Hodgkin’s lymphoma who received BEAM/Rituximab at the M. D. Anderson Cancer Center. We attempted to match these patients by age, donor-recipient gender, and donor-recipient CMV reactivity to a historical control of 44 patients with lymphoma, who received BEAM alone as a conditioning regimen, without the Rituximab. Tacrolimus and methotrexate were used for GVHD prophylaxis in both groups. A total of 10 patients in the study group, could be matched with 19 patients in the control group and were included in the final analysis. The outcome of the 2 groups is shown below: Rituximab-Study Group Control Group -value P No. of patients 10 19 Median age 41 44 0.4     (range) (19–55) (19–60) Patient-Donor sex-matched 9(82%) 18(95%) 0.6 Median # CD34 + cells infused (106/kg) 5.1 4.73 0.1 Patient or Donor CMV+ 9(82%) 18(95%) 0.6 Patient and Donor CMV − 1(10%) 1(5%) Median # prior chemoregimens 3 3 0.9     range (1–8) (1–9) Median follow-up 17 38     range (8–48) (27–77) Acute GVHD 2–4 (n,%) 5(50%) 7(37%) 0.5 Acute GVHD 3–4 (n,%) 3(30%) 5(26%) 0.6 Chronic GVHD (n, % cumulative incidence) 8 (90% + 15) 10 (53% + 12 0.01 Our data suggest that the described protective effect of Rituximab against GVHD in mouse models or in the setting of non-myeloablative allogeneic transplantation, may be overcome by the BEAM. This more intense conditioning regimen may induce more GVHD by enhancing T-cell cytokines release and by causing more gastrointestinal toxicity, thus allowing for a greater antigen presentation.

No Direct Effect of NOD2/CARD15 Variants On Clinical Outcome After Non-Myeloablative Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4322-4322
Author(s):  
Hanneke M. van der Straaten ◽  
Martine M. Paquay ◽  
Marcel G.J. Tilanus ◽  
Leo F. Verdonck ◽  
Cynthia Huisman
Keyword(s):  
Stem Cell ◽  
Clinical Outcome ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
Significant Prognostic Factor ◽  
Wild Type

Abstract Abstract 4322 Background Single nucleotide polymorphisms (SNPs) in the innate immunity receptor NOD2/CARD15 have been demonstrated to modulate the outcome of allogeneic haematopoietic stem cell transplantation. The effect of the NOD2/CARD15 polymorphism seems to be associated with donor source as well as type of conditioning regimen. Methods We reviewed NOD2/CARD15 mutations in all donor/recipient pairs of 192 consecutive patients who received non-myeloablative allogeneic stem cell transplantation(SCT) at our institution between 2002 and 2006. All patients were treated uniformly with fludarabine 30 mg/m2/day for 3 days followed by 200 cGy TBI (n=154) or TBI alone (n=38) and received grafts from HLA-matched related (n=132) or unrelated (n=60) donors. Results Mutated alleles were observed in 36 of 192 (19%) patients and in 35 of 192 (18%) donors. These SNPs, however, did not have a significant impact on clinical outcome data (P > 0.05, Kaplan Meier and Fine & Gray's test). Acute graft-versus-host disease (GVHD) occurred in 24 of 61 (39%) patients with the polymorphism and in 66 of 131 (50%) patients without the polymorphism. Chronic GVHD developed in 28 of 55 (51%) patients with SNP pairs and in 79 of 121 (65%) patients with the wild type. The incidence of transplant-related mortality was 21% in both groups, 13 of 61 patients in the group with the polymorphism and 27 of 131 without the polymorphism. Relapse was seen in 23 of 61 (38%) patients with the SNP pairs and in 48 of 131 (37%) wild type patients. Finally, overall survival was 43% (26/61) in patients with the polymorphism and 39% (51/131) in patients without the polymorphism. Conclusion These data indicate that mutations in the NOD2/CARD15 genes do not influence the clinical outcome of non-myeloablative allogeneic SCT directly. Since NOD2/CARD15 variants are not recognized as a single significant prognostic factor, screening for NOD2/CARD15 when selecting a donor does not seem to have additional value in patients undergoing non-myeloablative SCT. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation For Patients With Adrenoleukodystrophy. Nationwide Retrospective Study In Japan

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2148-2148
Author(s):  
Koji Kato ◽  
Hiromasa Yabe ◽  
Shunichi Kato ◽  
Souichi Adachi ◽  
Yoshiko Hashii ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Transplant Outcome

Abstract Introduction Adrenoleukodystrophy (ALD) is an autosomal recessive disorder with progressive neurodegeneration caused by the mutation of ABCD1 gene and allogeneic stem cell transplantation (SCT) at its early stage is recognized as the only effective treatment modality to control the neurological symptoms. But the transplant outcome according to the conditioning regimen is not well understood so far. Here we analyzed the transplant outcome of patients with ALD using the clinical data accumulated in the Japan Society of Hematopoietic Cell Transplantation and tried to find the favorable conditioning regimen. Methods From 1988 to 2010, 76 patients with ALD were transplanted and their age at transplant was 1-34 years old (median 8). Stem cell sources the patients received were bone marrow (sibling 26, non-sibling related donor 5, unrelated volunteer donor 17), and cord blood (sibling 1, unrelated 28). Conditioning regimen was classified into four categories of A: busulfan + cyclophosphamide +/- others, (n=25), B: melphalan + total lymphoid irradiation (TLI) / thoraco-abdominal irradiation (TAI) +/- fludarabine +/- anti-thymocyte globulin (n=23), C: fludarabine + melphalan +low dose total body irradiation (TBI) (n=18), and D: others (n=10). Results Sustained engraftment was obtained in 59 patients (77.8%) and it was significantly higher in bone marrow transplant (BMT) patients than cord blood transplant (CBT) patients (87.8% vs 60.7%, P=0.001). The incidence of acute graft-versus-host disease (GVHD), chronic GVHD and treatment related mortality of all patients were 7.9%, 19.3%, and 11.9%, respectively. Ten year overall survival (OS) and event free survival (EFS) of all patients were 83.7% and 64.1%, respectively. Ten patients died of either disease progression (n=2), or transplant related complications (n=8). Five year OS and EFS according to the conditioning regimen was A: 91.6% and 75.8%, B: 85.7% and 60.9%, C: 100% and 83.3%, D: 77.8% and 48.0%, respectively and they were not significant (P=0.379 in OS and P=0.183 in EFS, respectively). TBI was given to 22 patients with median dose of 4Gy (range 2-10.2) and sustained engraftment was obtained in 19 patients and all of 22 patients are alive. In patients who were not given TBI (n=54), 41 patients obtained engraftment and 44 patients are alive. OS according to presence or absence of TBI was 100% with TBI (n=22) and 86.1% without TBI (n=54) (P=0.091). By multivariate analysis for EFS, BMT and TBI were identified as good prognostic factors compared to CBT or non-TBI (HR 3.303, P=0.005, and HR 3.257, P=0.038, respectively), but OS of CBT was improved after 2005 compared to before 2004 (94.7% vs 68.6%, P=0.090). Conclusion Our results showed that conditioning regimen which includes TBI, even at low dose could provide better transplant outcome and the result of CBT improved after 2005 even though it was proved to be a significantly poor risk factor in the analysis of entire cohort. CBT enables urgent SCT when family donor is not available, and immediate transplant is essential for patients with ALD because of its nature. More precise assessment with brain MRI and neuropsychological examination is mandatory to evaluate the transplant outcomes of patients with ALD. Disclosures: No relevant conflicts of interest to declare.

Comparison Of Flow Cytometric and Clinical Findings In Patients With Paroxysmal Nocturnal Hemoglobinuria

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4877-4877
Author(s):  
Taner Demirer ◽  
Suphi Baslar ◽  
Vasif akin Uysal ◽  
Meral Beksac ◽  
Mehmet Ozen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Conditioning Regimen ◽  
Classical Type ◽  
Clone Size ◽  
Number Of Patients

Abstract Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare disorder of blood cells associated with mutations of X-linked gene called phosphatidylinositol glycan class A, and presenting as hemoglobinuria, signs of cytopenias (fatigue, easy bleeding) or thrombosis. In this study, 39 patients with PNH were retrospectively evaluated with regard to disease findings, laboratory investigations, complications and relationship between those and clone size. Median follow-up time was 26 months. Patients were divided into two groups. There were 24 classical PNH and 15 Aplastic Anemia (AA) or Myelodisplastic Syndrome (MDS) associated PNH patients. Evident signs of hemolysis at the time of diagnosis and thrombosis were seen in classical PNH patients. Sign of hemolysis developed in two AA patients. Hemoglobinuria, hemolysis test (increased reticulocyte and lactate dehydrogenase) were determined to be correlated with clone size. There was association between clone size and thrombosis. No patients with clone size smaller than 50% developed thrombosis and all patients with thrombosis were in classical PNH subtype which has greater clone size. PNH is a rare disease; therefore the effect of small number of patients on the statistical parameters must be taken into consideration. Over the entire course of follow-up time 8 patients died, 6 due to complications of allogeneic stem cell transplantation and 2 due to conditioning regimen before transplantation. Numbers of deaths are equal in each subtype. In summary, in this study there was a linear correlation between hemoglobinuria and LDH levels with clone size, which was statistically significant (p=0,031 and p=0,001 respectively). Other clinical signs did not correlate with clone size. Thrombotic complications were seen only in classical type PNH patients. No patients with clone size smaller than 50% developed thrombosis, MPV levels were significantly higher than others (p=0,04). There was also statistically significant correlation between reticulocyte and LDH levels with thrombotic events (p=0,009 and 0,003 respectively). In addition, after allogeneic stem cell transplantation 9 patients were evaluated for PNH clone and in 7 the clone was disappeared. Disclosures: No relevant conflicts of interest to declare.

Reduced intensity allogeneic stem cell transplantation in patients with myelodysplastic syndrome: Does the conditioning matter? A retrospective study of the SFGM-TC on 61 patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6547-6547
Author(s):  
L. Terriou ◽  
Z. Chir ◽  
H. Esperou ◽  
J. Boiron ◽  
N. Gratecos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
The Impact ◽  
Reduced Intensity

6547 Background: Reduced-intensity allogeneic stem cell transplantation (RIT) has emerged as an alternative to myeloablative transplantation in pts with myelodysplastic syndrome (MDS). Given the uncertainty regarding the appropriate conditioning, SFGM-TC conducted a retrospective multicenter study with the attempt to evaluate the impact of conditioning on pts’ outcome. Methods: The record of 61 pts (37 males) with MDS who received a RIT between 1998 and 2003, from 22 French transplantation centres, were reviewed. According to the FAB classification, 11 pts had RA at diagnosis, of whom one had progressed to REAB and one to AML before transplantation. Thirty-two pts had REAB, of whom 2 had progressed to REAB-T and 7 to AML. Twelve pts had REAB-T and 6 CMML, of whom 8 progressed to AML. The median time from diagnosis to RIT was 12 months (6–129). Conditioning regimen consisted of fludarabin (Flu) plus busulfan ( n=29), Flu plus 2-Gy TBI ( n=20) and idarubicin plus aracytine and Flu (n=12). Donors were HLA-identical siblings (n=52) and HLA-matched unrelated (n=9). All pts received peripheral blood stem cells. The median of CD34+ infused cell dose was 5 × 106/kg (0.5–17.3). Results: At the reference date of 1 July 2005, median follow-up was 44.7 months (21–85). Estimated 3-year overall survival (OS), progression free survival (PFS), relapse and transplant-relapse mortality (TRM) were 35%, 27%, 66% and 30%, respectively. Neither of the 3 conditioning regimens used had impact on pts’ outcome. In multivariable analyses, while acute III/IV grade GVHD development was the only factor found to adversely influencing OS (HR=3.6; 95% CI: 1.1–12.2), chronic GVHD development was the only favourably influencing PFS and relapse ratios (HR=0.3; 95% CI: 0.1–0.7 and HR=0.2; 95% CI: 0.1–0.6, respectively). TRM was adversely influenced by male sex of pt (HR=9.2; 95% CI: 1.5–66.6). Conclusions: RIT seems to be an effective treatment in MDS pts irrespective of conditioning type. While acute III/IV grade GVHD appeared to be detrimental, the benefit effect of chronic GVHD was to be bound to GVL effect. New approaches with focus on immunosuppressive treatment are needed to enhance the GVL effect with an acceptable risk of GVHD. No significant financial relationships to disclose.

Impact of antithymocyte globulin (ATG)-containing conditioning regimens on patients undergoing allogeneic stem cell transplantation (allo-CST) for poor risk cytogenetic IPSS myelodysplastic syndrome (PRC-MDS): A report from the French Society of Stem Cell Transplantation and Cell  Therapy (SFGM-TC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6542-6542
Author(s):  
Ibrahim Yakoub-Agha ◽  
Gandhi Laurent Damaj ◽  
Marie Robin ◽  
Stephane Vigouroux ◽  
Alice Garnier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
French Society ◽  
Poor Risk ◽  
Increased Risk

6542 Background: Due to a risk of relapse of underlying disease in patients with PRC-MDS, the use of ATG, incorporated within the conditioning regimen prior to allo-SCT, is still controversial. Methods: Inclusion criteria included patients aged over 18 (n=101) who received allo-SCT transplanted between 1999 and 2009 from either a sibling (n=68) or HLA-allele-MUD (10/10) (n=33) for PRC-MDS. HLA matching was double-checked by the national Bone Marrow Donor Registry. Results: According to the FAB/WHO classification at diagnosis, 22 pts had RA/RARS/RCMD, 40 RAEB1, 30 REAB2 and 9 RAEB-t/AML. 34 pts had progressed to a more advanced disease before allo-SCT. At diagnosis, 89 patients had an IPSS int-2 or higher. At transplant, 36 pts were responders (CR, PR, CRm) and 62 with progressive disease (relapsed/refractory, untreated or stable disease without hematological improvement). Median age at transplantation was 54 years (range, 22-69). Pts received myeloablative conditioning (n=46) and nonmyeloablative (n=55). In this series, 48 patients received ATG as part of conditioning ('ATG' group), whereas 53 did not ('no-ATG’ group). As of April 1st 2011, 44 patients died of relapse and 22 of TRM. 3-year relapse, overall and event-free survival rates were not significantly different between the two groups. In contrast, the cumulative incidence of grade 2-4 acute GVHD was 48% in the no-ATG group and 30% ATG group (P <.005). Although the cumulative incidence of chronic GVHD was similar in the no-ATG and ATG groups, a trend for a lower TRM was observed in the ATG group (p=.06). In multivariate analysis, the absence of use of ATG was associated with an increased risk of acute grade 2-4 [HR = 1.92, p=.044]. Conclusions: The addition of ATG to the conditioning regimen resulted in a decreased incidence of acute GVHD without increasing relapse rates and compromising survival of patients undergoing allo-SCT for poor risk cytogenetic MDS.

Secondary Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4297-4297
Author(s):  
Stefan Neuburger ◽  
Philipp Hemmati ◽  
Theis Terwey ◽  
Gero Massenkeil ◽  
Bernd Dörken ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Secondary Malignancies ◽  
Extensive Disease ◽  
Immunosupressive Therapy

Abstract Introduction: Allogeneic stem cell transplantation is a curative therapeutical option for patients (pts) with hematological diseases. As result of long term survival, late complications such as secondary malignancies are emerging. Methods: Here we present a retrospective analysis of 589 pts (median age at transplantation 41 years, range 16–75, male 339, female 250) who underwent allogeneic stem cell transplantation in our institution between 1995 and 2007 (siblings n= 285, unrelated donors n= 304). Pts suffered from acute leukemia (n= 257), chronic myeloproliferative disorders (n= 120), myelodysplastic syndrome (n= 39), non-hodgkin-lymphomas (n= 41) and others (n= 132). Pts received conditioning with (n= 436) or without (n=152) 12 Gy total body irradiation (TBI). Results: Up to 2007, 283 of 589 pts (48%) died of relapse or transplant related mortality (n=135 relapse, n= 84 infection, n= 36 graft-vs-host-disease (GVHD), n= 8 organ toxicity, n= 20 others or unknown). 305 out of 589 pts (52%) had survived with a median follow-up of 40 months (range 1–144 months). 21 out of 305 pts (6,9%) developed secondary malignancies at a mean of 5,1 years (range 1–10 years) after allogeneic stem cell transplantation. Localizations of secondary malignancies were skin (n= 11 basalioma, n= 2 melanoma), gut (n= 2 adenocarcinoma of the small intestine, n= 1 coloncarcinoma), oral cavity (n= 1 squamous cell cancer) and 3 lymphomas. 17/21 pts (81%) received a myeloablative conditioning with 12 Gy TBI, 4/21 pts (19%) a reduced intensity conditioning. Acute GVHD &gt; grade 2 and chronic GVHD extensive disease appeared in 48% and 67% respectively. Thus, these pts must be treated with prolonged immunosupressive therapy. 2/21 (9,5%) died of secondary malignancies (carcinoma of small intestine and colon) and one pts of accidential infection. Conclusion: Long term surviver of allogeneic stem cell transplantation are at increased risk of a secondary malignancies. Most of the pts received TBI-based conditioning and suffered from chronic GvHD extensive disease with consecutive immunosupressive therapy. Life-long follow-up will be needed to detect secondary malignancies in early stage of disease which might offer curative therapeutical options. Therefore, in our institution all pts undergo annual skin screening program and are sensitized for possibility of secondary malignancies late after transplantation.

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