Showing papers by "Eliane Gluckman published in 2008"

Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis

Abstract: Objective: Systemic sclerosis (SSc) is a generalised autoimmune disease, causing morbidity and a reduced life expectancy, especially in patients with rapidly progressive diffuse cutaneous SSc. As no proven treatment exists, autologous haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with a poor prognosis. This study reports the effects on survival, skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc. Patients and methods: A total of 26 patients were evaluated. Peripheral blood stem cells were collected using cyclophosphamide (4 g/m2) and rHu G-CSF (5 to 10 μg/kg/day) and were reinfused after positive CD34+ selection. For conditioning, cyclophosphamide 200 mg/kg was used. Results: After a median follow-up of 5.3 (1–7.5) years, 81% (n = 21/26) of the patients demonstrated a clinically beneficial response. The Kaplan–Meier estimated survival at 5 years was 96.2% (95% CI 89–100%) and at 7 years 84.8% (95% CI 70.2–100%) and event-free survival, defined as survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9–86%) at 5 years and 57.1% (95% CI 39.3–83%) at 7 years. Conclusion: This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation.

Clinical and Molecular Characteristics of Squamous Cell Carcinomas From Fanconi Anemia Patients

Abstract: Fanconi anemia is a recessively inherited disease that is characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck and anogenital regions. Previous studies of Fanconi anemia SCCs, mainly from US patients, revealed the presence of high-risk human papillomavirus (HPV) DNA in 21 (84%) of 25 tumors analyzed. We examined a panel of 21 SCCs mainly from European Fanconi anemia patients (n = 19 FA patients; 16 head and neck squamous cell carcinomas [HNSCCs], 2 esophageal SCCs, and 3 anogenital SCCs) for their clinical and molecular characteristics, including patterns of allelic loss, TP53 mutations, and the presence of HPV DNA by GP5+/6+ polymerase chain reaction. HPV DNA was detected in only two (10%) of 21 tumors (both anogenital SCCs) but in none of the 16 HNSCCs. Of the 18 tumors analyzed, 10 contained a TP53 mutation. The patterns of allelic loss were comparable to those generally found in sporadic SCCs. Our data show that HPV does not play a major role in squamous cell carcinogenesis in this cohort of Fanconi anemia patients and that the Fanconi anemia SCCs are genetically similar to sporadic SCCs despite having a different etiology.

Head and neck squamous cell carcinoma in 13 patients with Fanconi anemia after hematopoietic stem cell transplantation.

Abstract: BACKGROUND Fanconi anemia (FA) is a chromosomal instability disorder with a very high risk of developing head and neck squamous cell carcinoma (HNSCC), most notably after hematopoietic stem cell transplantation (HSCT) METHODS In the current study, the authors reported 13 cases of HNSCC in FA patients who underwent HSCT at the Saint Louis Hospital between 1976 and 2007 RESULTS The median age of the patients at time of HSCT was 97 years All patients received irradiation-based conditioning before HSCT and all developed extensive chronic graft versus host disease (GVHD) HNSCC was diagnosed at a median interval of 10 years after HSCT, mainly in numerous sites within the oral cavity (11 patients) Lymph node involvement was diagnosed in 4 patients The TNM classification was: T1 in 6 patients, T2 in 2 patients, T3 in 2 patients, and T4 in 3 patients Treatment was comprised of surgery in 10 patients, with clear surgical margins reported in 7 (including cervical lymph node dissection in 6 patients) Surgery was performed in addition to other treatments in only 2 patients (radiotherapy or cryotherapy) For the remaining 3 patients, treatment consisted in radiotherapy (2 patients) or chemotherapy (1 patient) Disease progression while receiving therapy was observed in 5 patients and 5 other patients developed disease recurrence between 35 and 237 months after treatment Death occurred in 11 patients At the time of last follow-up, only 2 patients were alive without any disease between 9 and 23 months after diagnosis CONCLUSIONS HNSCC developing in FA patients after HSCT is associated with a very poor prognosis A systematic surveillance of the oral cavity is essential to permit early surgery, which to the authors' knowledge remains the only curative treatment for a minority of patients It is very important to attempt to prevent this cancer by reducing chronic GVHD and using conditioning without irradiation Cancer 2008 © 2008 American Cancer Society

Patterns of Cytomegalovirus Reactivation Are Associated with Distinct Evolutive Profiles of Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract: T cell-mediated immunity is essential for the control of cytomegalovirus (CMV) infections in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aims were to identify patterns of CMV-specific immune responses associated with multiple or prolonged reactivations. We analyzed findings in 116 recipients during the course of infection or reactivation and latency. CD8(+) T cell responses were determined weekly, using HLA class I tetramers together with extended phenotypic analyses. Our results confirmed that recipients of allo-HSCT from unrelated donors were more susceptible to multiple reactivations and that the donor's CMV serological status influenced the occurrence of prolonged reactivations. We found that a lack of CMV-specific T cells after the first episode of reactivation was associated with multiple subsequent reactivations. In patients with uncontrolled reactivations, CMV-specific T cells of the late differentiation phenotype CD45RA(+)CD27(-)CD28(-) did not develop. Longitudinal evaluation of CD27 and CD45RA expression within the tetramer-positive subset could help identify patients in whom a protective immune response is developing. Evaluation of CMV-specific immune responses during the first episode of reactivation, together with extended phenotypes, could thus improve immune monitoring, especially in recipients at risk of uncontrolled viral reactivation.

Double cord blood transplantation in patients with high risk bone marrow failure syndromes.

Abstract: Summary Patients with bone marrow failure syndromes (BMFS) who reject a first allogeneic transplant or fail immunosuppressive therapy (IST) have an especially grim prognosis. We report 14 patients (eight adults, six children) transplanted with double cord blood transplantation (dUCBT) for BMFS. Neutrophil recovery was observed in eight patients, with full donor chimerism of one unit, and acute GVHD in 10. With a median follow-up of 23 months, the estimated 2 years overall survival was 80 ± 17% and 33 ± 16% for patients with acquired and inherited BMFS, respectively. Transplantation of two partially HLA-matched UCB thus enables salvage treatment of high-risk patients with BMFS.

Indications and results of cord blood transplant in children with leukemia.

Abstract: Umbilical cord blood transplant (UCBT) is now used more frequently for transplanting children with high-risk malignancies. The advantages are the rapid availability of donor cells, the possibility of using HLA-mismatched transplants and the decreased risk of acute and chronic GvHD. The Eurocord registry has collected and analyzed data on unrelated CBTs performed in European Blood and Marrow Transplant Group (EBMT) and non-EBMT centers. The literature shows that after UCBT relapse rate (RR), disease-free survival and overall survival of children with acute leukemia are similar to other hematopoietic stem cell sources (matched unrelated BM). Disease status at the time of transplantation is found in several studies to be a very important determinant of long-term outcome. In conclusion, UCB is a valuable alternative source of hematopoietic stem cell transplantation in children with acute leukemia who need an allogeneic transplant, but lack a suitable sibling donor.

Treatment of T-prolymphocytic leukemia with nonmyeloablative allogeneic stem cell transplantation: Minitransplant for T-prolymphocytic leukemia

Abstract: Abstract: Aim: T‐prolymphocytic leukemia (T‐PLL) is a rare disease of the elderly characterized by a high white blood cell count and organomegaly, and is currently incurable. Our aim was to elicit graft‐versus‐leukemia reactions in a patient with T‐PLL. Methods: A 52‐yr‐old woman with refractory T‐PLL underwent a nonmyeloablative regimen followed by allogeneic peripheral blood stem cell transplantation (a “minitransplant”) from her HLA‐matched sibling. Results: There was no treatment related toxicity other than neutropenia. Engraftment was successful. The patient experienced no graft‐versus‐host disease (GVHD) at any time but, on day 84 after transplantation, had a relapse in the central nervous system. Despite infusion of donor lymphocytes and intralumbar chemotherapy, she died on day 157 of systemic disease. Conclusion: The reasons why treatment may have failed are discussed (nature of disease, disease progression, treatment schedule).

Results of syngeneic hematopoietic stem cell transplantation for acute leukemia: risk factors for outcomes of adults transplanted in first complete remission

Abstract: Background 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.Design and Methods 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.Results 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).Conclusions 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.