Thymic recovery after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning is limited to patients younger than 60 years of age

in Haematologica (2011), 96(2)

Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning.

in Biology of Blood & Marrow Transplantation (2010), 16(6), 838-47

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD ... [more ▼]

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe. [less ▲]

Maladie du greffon contre l'hôte chronique : une prise en charge multidisciplinaire

in Revue Médicale de Liège (2010), 65

Chronic Graft-Versus-Host-Disease (GVHD) is a frequent complication of allogeneic hematopoietic cell transplantation. This review article describes recent advances in the classification and treatment of ... [more ▼]

Chronic Graft-Versus-Host-Disease (GVHD) is a frequent complication of allogeneic hematopoietic cell transplantation. This review article describes recent advances in the classification and treatment of chronic GVHD. [less ▲]

Non-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial.

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2009), 23(3), 608-10

Pulmonary veno-occlusive disease in myeloproliferative disorder.

in European Respiratory Journal (2009), 33(1), 213-216

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The ... [more ▼]

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The pulmonary disease evolved favourably under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic veno-occlusive disease. [less ▲]

Actualités thérapeutiques en hématologie.

in Revue Médicale de Liège (2007), 62(5-6), 384-90

This article focuses on recent advances in four important areas of hematology: aggressive lymphomas, allogeneic hematopoietic stem cell transplantation, multiple myeloma, and molecular therapy of cancer.

Infections after allogeneic hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen.

in Bone Marrow Transplantation (2006), 37(4), 411-8

Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed ... [more ▼]

Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed incidence and risk factors of infection in 62 patients undergoing NMSCT with low-dose TBI +/- fludarabine and postgrafting CsA and MMF. The proportion of patients with any infection was 77%, but the majority of infectious events occurred beyond day 30. Donor other than sibling, older age, early disease and male gender were significant risk factors. The incidence of bacteremia was 55% at 1 year and the number of bacteremic episodes was 0.9 per patient (0.08 before day 30). The risk of bacteremia increased with older age and the use of a donor other than an HLA-identical sibling, but not with neutropenia. The incidence of infections other than bacteremia correlated with the use of corticosteroids. The risk of CMV infection increased with high-risk CMV serology, and risk of CMV disease with high-risk CMV serology, older age, first transplantation and a diagnosis of lymphoma. In conclusion, after NMSCT, infections are not frequent in the first 30 days post transplant but careful long-term monitoring is necessary thereafter. [less ▲]

Pegfilgrastim compared with Filgrastim after autologous hematopoietic peripheral blood stem cell transplantation.

in Experimental hematology (2006), 34(3), 382-8

In order to assess the effect of Pegfilgrastim on the duration of neutropenia and clinical outcome of patients after autologous peripheral blood stem cell (PBSC) transplantation, we compared 20 ... [more ▼]

In order to assess the effect of Pegfilgrastim on the duration of neutropenia and clinical outcome of patients after autologous peripheral blood stem cell (PBSC) transplantation, we compared 20 consecutive patients with lymphoma or multiple myeloma receiving a single 6-mg dose of Pegfilgrastim on day 1 posttransplant to an historical control group of 60 patients receiving daily Filgrastim 5 microg/kg starting on day 1 posttransplant. The duration of neutropenia was similar in the Pegfilgrastim group compared with the control group. There were no differences in time to neutrophil, erythroid, or platelet engraftment nor in the incidence of fever and infections. The duration of antibiotic therapy, transfusion support, and time to hospital discharge were similar in the two groups. However, after initial hematopoietic reconstitution, we observed significantly higher values of lymphocytes (e.g., 1,660+/-1,000 versus 970+/-460 on day 80, p=0.0002), neutrophils (e.g., 3,880+/-2,030 versus 2,420+/-1,500 on day 25, p=0.0004), reticulocytes (e.g., 148,160+/-90,590 versus 87,140+/-65,920 on day 25, p<0.0001), and platelets (e.g., 210,700+/-116,090 versus 150,240+/-58,230 on day 55, p=0.0052) up to day 100 in the Pegfilgrastim group compared with the Filgrastim group. These observations had no impact on clinical outcome of the patients after day 30 due to the low incidence of infectious events after engraftment in autologous PBSC transplantation. We conclude that the effect of Pegfilgrastim administrated on day 1 posttransplant is comparable to that of daily Filgrastim on initial hematopoietic reconstitution. The possibly superior effect of Pegfilgrastim on cell counts we observed after initial engraftment should be further tested in a prospective randomized trial. [less ▲]

Specific innervation of aromatase neurons by substance P fibers in the dorsal horn of the spinal cord in quail

in Journal of Comparative Neurology (2003), 465(2), 309-318

The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in ... [more ▼]

The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in this area and the control of spinal aromatase activity is thought to play an important role in the estrogenic control of nociception. The coexistence of aromatase and nociceptive terminals suggests a role for aromatase cells in pain-related processes, but whether terminals releasing nociceptive neuropeptides (e.g., substance P) actually contact aromatase neurons is unknown and the factors that control spinal aromatase activity have not yet been identified. In the present study we analyzed by double-label immunocytochemistry the distribution in the Japanese quail spinal cord, of aromatase and of substance P or its receptor (neurokinin 1 receptor). All antigens were mainly localized in laminae I and II as observed in mammals. Most aromatase neurons were colocalized with neurokinin 1 receptors and were in close apposition with substance P-immunoreactive fibers. These results suggest that aromatase neurons are responsive to noxious stimulation and may participate in the control of nociception. Furthermore, spinal aromatase activity could be controlled by substance P through a regulation of the aromatase gene transcription as reported for the mouse diencephalon and/or through neurokinin 1 receptor-dependent phosphorylation of the aromatase protein. [less ▲]

Peut-on prevenir le developpement du cancer prostatique?

in Revue Médicale de Liège (2003), 58(4), 240-6

Prostate cancer is the most frequent cancer in men living in industrialized countries. Numerous epidemiological and laboratory studies suggest that various hereditary, toxic, hormonal, and dietary factors ... [more ▼]

Prostate cancer is the most frequent cancer in men living in industrialized countries. Numerous epidemiological and laboratory studies suggest that various hereditary, toxic, hormonal, and dietary factors may be involved in the development and/or progression of prostate cancer lesions. Several large prospective randomized trials for the chemo-prevention of prostate cancer are currently ongoing. In this review, data regarding the implication of dietary factors have been analyzed under the light of recent literature in order to determine whether proven efficient prevention is available today. [less ▲]