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ABSTRACT: Mesenchymal stromal cells (MSC) are multipotent adult stem cells with the potential to regenerate tissue damage and inhibit inflammation and fibrosis in parallel. As they are non-immunogenic, MSC can be safely auto- and allotransplanted and consequently represent a therapeutic option for refractory connective tissue diseases and fistulizing colitis like Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, 22 are on autoimmune diseases and 27 are actually recruiting bowel disease' patients. More than 1,500 patients with bowel diseases like Crohn's disease were treated in clinical trials by local as well as systemic MSC therapy. Phase I and II trials on fistula documented the feasibility and safety of MSC therapy, and a significant superiority compared to fibrin glue in fistulizing bowel diseases was demonstrated. Autologous as well as allogeneic use of Bone marrow as well as of adipose tissue-derived MSC are feasible. In refractory Graft versus host disease, especially in refractory gut Graft versus host diseases, encouraging results were reported using MSC. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets toward an increase in T regulatory cells and a decrease in activated effector T cells. Mesenchymal stem cells represent a safe therapy for patients with refractory inflammatory bowel diseases.
Immunologic Research 04/2013; · 3.03 Impact Factor
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ABSTRACT: Mesenchymal stem cells (MSC), multipotent adult stem cells, feature the potential to regenerate tissue damage and, in parallel, inhibit inflammation and fibrosis. MSC can be safely transplanted in autologous and allogeneic ways as they are non-immunogenic, and consequently represent a therapeutic option for refractory connective tissue diseases, fibrosing diseases like scleroderma and fistulizing colitis like in Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, and 22 are on autoimmune diseases. In irradiation-induced colitis, MSC accelerate functional recovery of the intestine and dampen the systemic inflammatory response. In order to provide rescue therapy for accidentally over-irradiated prostate cancer patients who underwent radiotherapy, allogeneic bone marrow-derived MSC from family donors were intravenously infused to three patients with refractory and fistulizing colitis resembling fistulizing Crohn's disease. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhoea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets towards an increase of T regulatory cells and a decrease of activated effector T cells. The current data indicate that MSC represent a promising alternative strategy in the treatment of various immune-mediated diseases. Encouraging results have already been obtained from clinical trials in Crohn's disease and SLE as well as from case series in systemic sclerosis. MSC represent a safe therapeutic measure for patients who suffer from chronic and fistulizing colitis. These findings are instructional for the management of refractory inflammatory bowel diseases that are characterized by similar clinical and immunopathological features.
Clinical Reviews in Allergy & Immunology 01/2013; · 3.68 Impact Factor
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Laurent Garderet,
Simona Iacobelli,
Philippe Moreau,
Mamoun Dib,
Ingrid Lafon,
Dietger Niederwieser,
Tamas Masszi,
Jean Fontan,
Mauricette Michallet,
Alois Gratwohl, [......],
Nicolas Ketterer,
Christian Koenecke,
Marleen van Os,
Mohamad Mohty,
Andrew Cakana, Norbert Claude Gorin,
Theo de Witte,
Jean Luc Harousseau,
Curly Morris,
Gösta Gahrton
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ABSTRACT: This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT).
Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months).
Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 25%; P = .001), and the median duration of response was longer (17.2 v 13.4 months; P = .03). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia.
VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.
Journal of Clinical Oncology 05/2012; 30(20):2475-82. · 18.37 Impact Factor
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Olle Ringdén,
Myriam Labopin, Norbert-Claude Gorin,
Liisa Volin,
Giovanni F Torelli,
Michel Attal,
Jean P Jouet,
Noel Milpied,
Gerard Socié,
Catherine Cordonnier,
Mauricette Michallet,
Arturo I Atienza,
Olivier Hermine,
Mohamad Mohty
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ABSTRACT: This study analysed the effects of growth factor on outcome after haematopoietic stem-cell transplantation (HSCT) with >9 years follow-up. Of 1887 adult patients with acute leukaemia who received bone marrow from human leucocyte antigen (HLA)-identical siblings and were treated with myeloablative conditioning, 459 (24%) were treated with growth factor. Growth factor hastened engraftment of neutrophils (P < 0·0001), but reduced platelet counts (P = 0·0002). Graft-versus-host disease (GVHD)-free survival (no acute GVHD grade II-IV or chronic GVHD) at 10 years was 12 ± 2% (±SE) in the growth factor group, as opposed to 17 ± 2% in the controls [hazard ratio (HR) 0·81, P = 0·001]. Similar differences in GVHD-free survival were seen in patients with or without conditioning with total body irradiation (TBI). Non-relapse mortality (NRM) was higher in the growth factor group irrespective of whether or not TBI conditioning was included [HR = 1·48; 95% confidence interval (CI): 1·15-1·9; P = 0·002; HR = 1·59; 95% CI: 1·07-2·37; P = 0·02, respectively]. Both groups had similar probabilities of leukaemic relapse (HR = 0·96; 95% CI: 0·78-1·18; P = 0·71). Leukaemia-free survival (LFS) at 10 years was 35 ± 2% in those receiving growth factor prophylaxis, as opposed to 44 ± 1% in the controls (HR = 0·70; 95% CI: 0·60-0·82; P = 0·00001). Prophylaxis with growth factor increases the risk of GVHD, does not affect relapse, increases NRM and reduces LFS > 10 years after HSCT, regardless of conditioning with TBI.
British Journal of Haematology 02/2012; 157(2):220-9. · 4.94 Impact Factor
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Norbert-Claude Gorin,
Myriam Labopin,
Josy Reiffers,
Noel Milpied,
Didier Blaise,
Francis Witz,
Theo de Witte,
Giovanna Meloni,
Michel Attal,
Teresa Bernal,
Vanderson Rocha
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ABSTRACT: The stem cell source for autologous transplantation has shifted from bone marrow to peripheral blood (PB). We previously showed that relapse incidence in patients with acute myelocytic leukemia autografted in first remission (CR1) was greater with PB than bone marrow, and a poorer outcome was associated with a shorter CR1 to PB transplantation interval (≤ 80 days). Leukemic and normal progenitors are CD34(+) and can be concomitantly mobilized; we assessed whether an association exists between the infused CD34(+) cell dose and outcome. The infused CD34(+) cell doses were available for 772 patients autografted more than 80 days after CR1 and were categorized by percentiles. We selected the highest quintile (> 7.16 × 10(6)/kg) as the cutoff point. By multivariate analysis, relapse was more probable in patients who received the highest dose (hazard ratio = 1.48; 95% confidence interval, 1.12-1.95; P = .005), and leukemia-free survival was worse (hazard ratio = 0.72; 95% confidence interval, 0.55-0.93; P = .01). In conclusion, in patients autografted in first remission, relapse was higher and leukemia-free survival lower for those who received the highest CD34(+) PB doses.
Blood 10/2010; 116(17):3157-62. · 9.90 Impact Factor
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ABSTRACT: A European consensus concerning the medical management of mass radiation exposure was obtained in 2005 during a conference held by the European Group for Blood and Bone Marrow Transplantation, the Institute of Radioprotection and Nuclear Safety, and the University of Ulm. At the conference, a two-step triage strategy to deal with large masses of radiation-exposed patients was designed. The first step of this strategy concerns the first 48 h and involves scoring the patients exclusively on the basis of their clinical symptoms and biological data. This allows the non-irradiated bystanders and outpatient candidates to be identified. The remaining patients are hospitalized and diagnosis is confirmed after the first 48-h period according to the METREPOL (Medical Treatment Protocols for radiation accident victims) scale. This grades the patients according to the severity of their symptoms. It was also agreed that in the case of acute radiation syndrome (ARS), emergency hematopoietic stem cell (HSC) transplantation is not necessary. Instead, cytokines that promote hematological reconstruction should be administered as early as possible for 14-21 d. Crucial tests for determining whether the patient has residual hematopoiesis are physical dose reconstructions combined with daily blood count analyses. It was agreed that HSC transplantation should only be considered if severe aplasia persists after cytokine treatment. Two recent cases of accidental radiation exposure that were managed successfully by following the European consensus with modification are reviewed here. Thus, a European standard for the evaluation and treatment of ARS victims is now available. This standard may be suitable for application around the world.
Health physics 06/2010; 98(6):825-32. · 0.92 Impact Factor
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Journal of Clinical Oncology 04/2010; · 18.37 Impact Factor
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Charalampia Kyriakou,
Carmen Canals,
David Sibon,
Jean Yves Cahn,
Majid Kazmi,
William Arcese,
Karin Kolbe, Norbert Claude Gorin,
Kristy Thomson,
Noel Milpied,
Dietger Niederwieser,
Karel Indrák,
Paolo Corradini,
Anna Sureda,
Norbert Schmitz
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ABSTRACT: The role of autologous stem-cell transplantation (ASCT) in Waldenström macroglobulinemia (WM) is not defined. The aim of this study was to analyze the results of ASCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome.
We analyzed 158 adult patients with WM reported to the European Group for Blood and Marrow Transplantation (EBMT) between January 1991 and December 2005. Median time from diagnosis to ASCT was 1.7 years (range, 0.3 to 20.3 years), 32% of the patients experienced treatment failure with at least three lines of therapy, and 93% had sensitive disease at the time of ASCT. Conditioning regimen was total-body irradiation-based in 45 patients. Median follow-up for surviving patients was 4.2 years (range, 0.5 to 14.8 years).
Nonrelapse mortality was 3.8% at 1 year. Ten patients developed a secondary malignancy, with a cumulative incidence of 8.4% at 5 years. Relapse rate was 52.1% at 5 years. Progression-free survival (PFS) and overall survival were 39.7% and 68.5%, respectively, at 5 years and were significantly influenced by number of lines of therapy and chemorefractoriness at ASCT. The achievement of a negative immunofixation after ASCT had a positive impact on PFS after ASCT. When used as consolidation at first response, ASCT provided a PFS of 44% at 5 years.
ASCT is a feasible procedure in young patients with advanced WM. ASCT should not be offered to patients with chemoresistant disease and to those who received more than three lines of therapy.
Journal of Clinical Oncology 04/2010; 28(13):2227-32. · 18.37 Impact Factor
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Karin Tarte,
Julien Gaillard,
Jean-Jacques Lataillade,
Loic Fouillard,
Martine Becker,
Hossein Mossafa,
Andrei Tchirkov,
Hélène Rouard,
Catherine Henry,
Marie Splingard,
Joelle Dulong,
Delphine Monnier,
Patrick Gourmelon, Norbert-Claude Gorin,
Luc Sensebé
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ABSTRACT: Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.
Blood 02/2010; 115(8):1549-53. · 9.90 Impact Factor
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American Journal of Hematology 01/2010; 85(11):891. · 4.67 Impact Factor
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ABSTRACT: Anemia is a characteristic of myelodysplastic syndromes, such as the rare 5q- syndrome, but its mechanism remains unclear. In particular, data are lacking on the terminal phase of differentiation of erythroid cells (enucleation) in myelodysplastic syndromes.
We used a previously published culture model to generate mature red blood cells in vitro from human hematopoietic progenitor cells in order to study the pathophysiology of the 5q- syndrome. Our model enables analysis of cell proliferation and differentiation at a single cell level and determination of the enucleation capacity of erythroid precursors.
The erythroid commitment of 5q(del) clones was not altered and their terminal differentiation capacity was preserved since they achieved final erythroid maturation (enucleation stage). The drop in red blood cell production was secondary to the decrease in the erythroid progenitor cell pool and to impaired proliferative capacity. RPS14 gene haploinsufficiency was related to defective erythroid proliferation but not to differentiation capacity.
The 5q- syndrome should be considered a quantitative rather than qualitative bone marrow defect. This observation might open the way to new therapeutic concepts.
Haematologica 10/2009; 95(3):398-405. · 6.42 Impact Factor
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Olle Ringdén,
Myriam Labopin,
Gerhard Ehninger,
Dietger Niederwieser,
Richard Olsson,
Nadezda Basara,
Juergen Finke,
Rainer Schwerdtfeger,
Matthias Eder,
Donald Bunjes, Norbert-Claude Gorin,
Mohamad Mohty,
Vanderson Rocha
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ABSTRACT: Reduced intensity conditioning regimen (RIC) is increasingly used in hematopoietic stem cell transplantation (HSCT). Unrelated donor (UD) transplants have more complications. We wanted to examine if RIC is a valid treatment option using UD in acute myeloblastic leukemia (AML).
Between 1999 and 2005, 401 patients with AML were treated with RIC and 1,154 received myeloablative conditioning (MAC), using UD and reported to the European Group for Blood and Marrow Transplantation Registry. Patients < and > or = 50 years of age were analyzed separately.
Patients receiving RIC were older, received transplants more recently, received peripheral blood stem cells more frequently, and were treated with total-body irradiation less often. In multivariable analysis, in patients younger than 50 years of age, nonrelapse mortality (NRM) was similar using RIC (hazard ratio [HR], 0.85; P = .41), relapse was increased (HR, 1.46; P = .02) and leukemia-free survival (LFS) was the same (HR, 0.88; P = .28), as compared with MAC. In patients > or = 50 years of age, NRM was decreased in the RIC group (HR, 0.64; P = .04), relapse probability was not significantly different (HR, 1.34; P = .16) and LFS was similar (HR, 1.04; P = .79) compared with MAC. CONCLUSION RIC-UD transplants are associated with higher relapse in AML patients younger than 50 years of age and decreased NRM in those > or = 50 years compared with MAC-UD. LFS was similar after both conditioning regimens, regardless of age. Therefore, RIC-UD extend the use of allotransplants for elderly patients and strategies that decrease relapse should be considered mainly in younger patients with AML.
Journal of Clinical Oncology 09/2009; 27(27):4570-7. · 18.37 Impact Factor
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Lucie Oberic,
Marc Buffet,
Mickael Schwarzinger,
Agnès Veyradier,
Karine Clabault,
Sandrine Malot,
Nicolas Schleinitz,
Dominique Valla,
Lionel Galicier,
Leila Bengrine-Lefèvre, Norbert-Claude Gorin,
Paul Coppo
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ABSTRACT: To specify the clinical and biological characteristics of thrombotic microangiopathies (TMAs) associated with a recent diagnosis of cancer. PATIENTS AND Methods. Multicenter study involving 14 national centers. Cross-sectional analysis of 20 patients with cancer-associated TMAs included in our national registry from October 2000 to July 2007. Patients were also compared with 134 adult patients with an acquired idiopathic TMA by univariate analysis.
Patients with a cancer-associated TMA typically displayed severe weight loss, dyspnea, bone pain, as well as disseminated intravascular coagulopathy and massive erythromyelemia (75%, 55%, 50%, 41%, and 85% of cases, respectively). By contrast, these features were observed with a much lower incidence in patients with an idiopathic TMA (8.9%, 19.7%, 0.8%, 7.1%, and 17.5%, respectively). Moreover, median platelet count was higher (48 x 10(9)/l; range, 21-73 x 10(9)/l versus 19 x 10(9)/l; range, 10-38 x 10(9)/l, respectively) and median serum creatinine level was lower (74 microM [range, 68-102] versus 113 microM [range, 80-225], respectively). The activity of the specific von Willebrand factor-cleaving proteinase ADAMTS13 was detectable in 14/17 studied patients. Platelet count improvement was observed in only seven patients and paralleled the response to chemotherapy. Prognosis of patients with cancer-associated TMAs was very poor, with a 30-day and 2-year mortality rate of 50% and 95%, respectively.
Cancer-associated TMAs display specific features at onset that should prompt investigation of an underlying disseminated malignancy. In this context, chemotherapy rather than plasma is mandatory since TMA prognosis parallels that of cancer.
The Oncologist 09/2009; 14(8):769-79. · 3.91 Impact Factor
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Norbert-Claude Gorin,
Myriam Labopin,
Didier Blaise,
Josy Reiffers,
Giovanna Meloni,
Mauricette Michallet,
Theo de Witte,
Michel Attal,
Bernard Rio,
Francois Witz,
Loic Fouillard,
Roel Willemze,
Vanderson Rocha
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ABSTRACT: The cell source for autologous stem cell transplantation has shifted from bone marrow (BM) to peripheral blood (PB). In acute myelocytic leukemia (AML), for patients who receive transplants during first complete remission (CR1), no prospective randomized study has compared relapse incidence (RI) to cell source.
We analyzed 2,165 patients who received autografts (1,607 PB and 558 BM) from 1994 to 2006 and were reported to the European Cooperative Group for Blood and Marrow Transplantation with complete research data. Relative to the time of CR1, PB transplants were performed earlier than BM transplants. Because a poorer outcome was associated with a shorter interval from CR1 to transplantation, patients were divided into three groups: BM, early PB (< or = 80 days after CR1), and late PB (> 80 days after CR1) transplantation.
In a multivariate analysis adjusted for differences between groups and center, RI was higher with both early PB (56% +/- 3%; hazard ratio [HR], 1.45; 95% CI, 1.11 to 1.9; P = .006) and late PB transplantation (46% +/- 2%; HR, 1.3; 95% CI, 1.06 to 1.59; P = .01) as compared with BM transplantation (39% +/- 2%). This translated into a significantly worse leukemia-free survival (LFS) for early PB transplantation (36% +/- 3%; HR, 0.75; 95% CI, 0.58 to 0.96; P = .02) and a trend for a poorer LFS for late PB (46% +/- 2%; HR, 0.84; 95% CI, 0.7 to 1.01; P = .06) as compared with BM (52% +/- 2%).
For patients with AML in CR1, risk of relapse is greater with PB transplantation rather than BM, independent of the interval from CR1 to transplantation.
Journal of Clinical Oncology 08/2009; 27(24):3987-93. · 18.37 Impact Factor
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Paul Coppo,
Valérie Gouilleux-Gruart,
Yenlin Huang,
Hicham Bouhlal,
Hakim Bouamar,
Sandrine Bouchet,
Christine Perrot,
Vincent Vieillard,
Peggy Dartigues,
Philippe Gaulard,
Félix Agbalika,
Luc Douay,
Kaiss Lassoued, Norbert-Claude Gorin
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ABSTRACT: Nasal-type natural killer (NK) cell lymphoma is an infrequent aggressive malignant disease with very poor prognosis. We aimed to explore the possible role of the transcription factor STAT3 in the pathophysiology of this malignancy, as it was involved in oncogenesis and chemoresistance. For this, we established and characterized a continuous interleukin 2-dependent NK cell line (MEC04) from a patient with a fatal nasal-type NK-cell lymphoma. Cells harbored poor cytotoxic activity against K562 cells, and spontaneously secreted interferon-gamma, interleukin-10 and vascular-endothelium growth factor in vitro. STAT3 was phosphorylated in Y705 dimerization residue in MEC04 cells and restricted to the nucleus. Y705 STAT3 phosphorylation involved JAK2, as exposure of cells to AG490 inhibitor inhibited Y705 STAT3 phosphorylation. By using recombinant transducible TAT-STAT3-beta (beta isoform), TAT-STAT3Y705F (a STAT3 protein mutated on Y705 residue, which prevents STAT3 dimerization) and peptides inhibiting specifically STAT3 dimerization, we inhibited STAT3 phosphorylation and cell growth, with cell death induction. Finally, STAT3 was phosphorylated in Y705 residue in the nuclei of lymphoma cells in eight/nine patients with nasal-type NK/T-cell lymphoma and in YT, another NK cell line. Our results suggest that STAT3 protein has a major role in the oncogenic process of nasal-type NK-cell lymphomas, and may represent a promising therapeutical target.
Leukemia 05/2009; · 9.56 Impact Factor
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Theodor M Fliedner,
Nelson J Chao,
Judith L Bader,
Axel Boettger,
Cullen Case,
John Chute,
Dennis L Confer,
Arnold Ganser, Norbert-Claude Gorin,
Patrick Gourmelon,
Dieter H Graessle,
Robert Krawisz,
Viktor Meineke,
Dietger Niederwieser,
Matthias Port,
Ray Powles,
Bhawna Sirohi,
David M Weinstock,
Albert Wiley,
C Norman Coleman
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ABSTRACT: The concern of the public regarding terrorist actions involving nuclear emergencies resulted in the reopening of the discussion regarding the best ways to cope with the inevitable health impairments. Medical experts from the US and from Europe considered it of importance to harmonize at an international level the diagnostic and therapeutic approaches regarding the radiation-induced health impairments. The present contribution is the result of the first U.S./European Consultation Workshop addressing approaches to radiation emergency preparedness and assistance, which was held recently at Ulm University, Ulm, Germany. Discussions dealt with the assessment of the extent of damage after total body exposure and, in particular, the quantity and quality of the damage to the hematopoietic stem cell pool. Secondly, the pathogenesis of the multiorgan failure was considered because of the organ-to-organ interactions. Thirdly, approaches were considered to harmonize the "triage-methods" used on an international level using the "Response Category" approach as developed for the European Communities. These discussions lead to the conclusion that there is a strong need for continuing education of physicians, nurses, and support personnel to address the issues posed by the management of patients suffering from radiation syndromes. Finally, the discussions expressed the need for more international cooperation in research and development of more refined methods to treat patients with any type of radiation syndromes.
Stem Cells 02/2009; 27(5):1205-11. · 7.78 Impact Factor
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Norbert-Claude Gorin,
Myriam Labopin,
Francesco Frassoni,
Noel Milpied,
Michel Attal,
Didier Blaise,
Giovanna Meloni,
Anna P Iori,
Mauricette Michallet,
Roel Willemze,
Eric Deconninck,
Jean-Luc Harousseau,
Emmanuelle Polge,
Vanderson Rocha
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ABSTRACT: Patients with acute myelocytic leukemia carrying inversion 16 (inv16) or t(8;21) have a better initial response to high-dose cytarabine than patients without these chromosomal abnormalities. They presently do not undergo transplantation in first remission (CR1), but there is concern about late relapses.
From 1990 to 2004, 325 adult patients received transplantations in CR1 (159 patients with inv16 and 166 patients with t(8;21), including 35 and 60 patients, respectively, with additional chromosomal abnormalities). Genoidentical allografts were performed in 64 patients with inv16 and 81 patients with t(8;21), and autografts were performed in 95 patients with inv16 and 85 patients with t(8;21).
In patients with inv16, after allogeneic and autologous transplantation, the 5-year leukemia-free survival (LFS) rates were 59% and 66% (P = .5), the relapse incidence (RI) rates were 27% and 32% (P = .45), and the transplantation-related mortality (TRM) rates were 14% and 2% (P = .003), respectively. Female patients had a lower RI and a higher LFS. Additional chromosomal abnormalities, compared with no additional abnormalities, were associated with lower RI rate (12% v 34%, respectively; P = .01) and higher 5-year LFS rate (78% v 59%, respectively; P = .04). In patients with t(8;21), after allogeneic and autologous transplantation, the 5-year LFS rates were 60% and 66% (P = .69), the RI rates were 15% and 28% (P = .03), and the TRM rates were 24% and 6% (P = .003), respectively. Younger age and a lower WBC count at diagnosis were associated with a lower TRM and a better LFS. The TRM was lower and the RI was higher in patients with autologous transplantations versus allogeneic transplantations.
Both autologous and allogeneic transplantation resulted in similar outcomes.
Journal of Clinical Oncology 08/2008; 26(19):3183-8. · 18.37 Impact Factor
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Loic Fouillard,
Myriam Labopin,
Alois Gratwohl,
Eliane Gluckman,
Francesco Frassoni,
Dietrich W Beelen,
Roelof Willemze,
Emili Montserrat,
Didier Blaise,
Arturo Iriondo Atienza,
Jorge Sierra,
Moema Santos, Norbert-Claude Gorin,
Vanderson Rocha
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ABSTRACT: The possibility of performing syngeneic hematopoietic stem cell transplantation is rare and there are concerns about the absence of a graft-versus-leukemia effect following such a strategy. We report the outcomes of a large series of adult patients who underwent syngeneic hematopoietic stem cell transplantation for acute myeloblastic leukemia or acute lymphoblastic leukemia.
The outcomes of all syngeneic transplants for acute myeloblastic or lymphoblastic leukemia reported to the European Group for Blood and Marrow Transplantation registry were analyzed; a study of prognostic factors was performed for those transplanted in first complete remission.
One hundred and sixty-two patients, 109 with acute myeloblastic leukemia and 53 with acute lymphoblastic leukemia, were identified; 116 were in first complete remission. Most of the patients did not receive prophylaxis against graft-versus-host disease. Nineteen patients developed acute graft-versus-host disease and only three patients developed chronic graft-versus-host disease. The median follow-up was 60 months. At 5 years the non-relapse mortality was 8 +/- 5%, the relapse incidence 49 +/- 8% and the leukemia-free survival 43 +/- 3%. The corresponding figures for patients in first complete remission were 7 +/- 2%, 40 +/- 4% and 53 +/- 5% at 5 years. Analysis of patients in first complete remission showed that the number of courses of chemotherapy required to induce first complete remission was the main risk factor: the leukemia-free survival at 5 years was 66 +/- 6% when first complete remission was reached after one induction course of chemotherapy and was only 20 +/- 9% when first complete remission was reached after at least two induction courses of chemotherapy (p = 0.0001); the relapse incidence was 30 +/- 6% and 54 +/- 10%, respectively (p = 0.007).
Outcomes were better for patients transplanted in first complete remission than in second complete remission or a more advanced phase of the disease. When a syngeneic donor is available for patients with high risk acute leukemia, allotransplantation should be performed as soon as the first complete remission has been achieved, ideally with one course of chemotherapy.
Haematologica 07/2008; 93(6):834-41. · 6.42 Impact Factor
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ABSTRACT: The treatment of elderly patients with multiple myeloma was based for the last forty years on the combination of alkeran plus prednisone. The survival was short. Three new molecules, thalidomide, bortezomib and revlimid are completely changing the way we treat myeloma as well as the prognosis. These new molecules are tested either alone or in combination. The addition of thalidomide to alkeran plus prednisone has increased overall survival of two years. For the first time, major therapeutic improvements are emerging giving rise to better prognosis.
Bulletin du cancer 05/2008; 95 FMC Onco:F84-8. · 0.67 Impact Factor
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Christoph Schmid,
Myriam Labopin,
Arnon Nagler,
Martin Bornhäuser,
Jürgen Finke,
Athanasios Fassas,
Liisa Volin,
Günham Gürman,
Johan Maertens,
Pierre Bordigoni,
Ernst Holler,
Gerhard Ehninger,
Emmanuelle Polge, Norbert-Claude Gorin,
Hans-Jochem Kolb,
Vanderson Rocha
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ABSTRACT: To evaluate the role of donor lymphocyte infusion (DLI) in the treatment of relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT).
We retrospectively analyzed the data of 399 patients with AML in first hematological relapse after HSCT whose treatment did (n = 171) or did not (n = 228) include DLI. After correction for imbalances and established risk factors, the two groups were compared with respect to overall survival. Further, a detailed analysis of risk factors for survival among DLI recipients was performed.
Median follow-up was 27 and 40 months, respectively. Estimated survival at 2 years (+/- standard deviation) was 21% +/- 3% for patients receiving DLI and 9% +/- 2% for patients not receiving DLI. After adjustment for differences between the groups, better outcome was associated with age younger than 37 years (P = .008), relapse occurring more than 5 months after HSCT (P < .0001), and use of DLI (P = .04). Among DLI recipients, a lower tumor burden at relapse (< 35% of bone marrow blasts; P = .006), female sex (P = .02), favorable cytogenetics (P = .004), and remission at time of DLI (P < .0001) were predictive for survival in a multivariate analysis. Two-year survival was 56% +/- 10%, if DLI was performed in remission or with favorable karyotype, and 15% +/- 3% if DLI was given in aplasia or with active disease.
Although further evidence for a graft-versus-leukemia effect by DLI is provided, our results confirm, that the clinical benefit is limited to a minority of patients. Strategies to reduce tumor burden before DLI, as well as alternative treatment options should be investigated in adults with relapsed AML after HSCT.
Journal of Clinical Oncology 12/2007; 25(31):4938-45. · 18.37 Impact Factor
