Allogeneic stem cell transplantation for chronic myelomonocytic leukemia : a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire
; ; et al
in European Journal of Haematology (2013), 90
Objectives and methods: Chronic myelomonocytic leukemia (CMML) is a severe disease for which allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative treatment. We describe a ... [more ▼]
Objectives and methods: Chronic myelomonocytic leukemia (CMML) is a severe disease for which allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative treatment. We describe a retrospective study determining prognostic factors for outcome after allo-SCT in consecutive 73 patients with CMML reported to the SFGM-TC registry between 1992 and 2009. Results: At diagnosis, median age was 53 yrs, and 36% patients had palpable splenomegaly (SPM). 48, 13, and 9 patients had good, intermediate, and poor risk karyotype, respectively, according to IPSS, 61% patients had CMML-1, and 39% had CMML-2. 41/31/1 cases had an HLA-identical sibling, an unrelated and haploidentical donor, respectively. 43 patients received reduced-intensity conditioning. With a median follow-up of 23 month, acute grade 2–4 and chronic GVHD developed in 21 and 25 patients, respectively. The 3-year OS, NRM (non-relapse mortality),EFS, and CIR (cumulative incidence of relapse) were 32%, 36%, 29% and 35%, respectively. OS was not influenced by the CR status, marrow blasts% at allo-SCT, prior treatments, and cGVHD. Using multivariate analysis, year of transplant < 2004 (YOT) (P = 0.005) was associated with higher NRM, YOT < 2004 (P = 0.04) and SPM at allo-SCT (P = 0.02) with lower EFS, and YOT < 2004 (P = 0.03) and SPM at allo-SCT (P = 0.04) with poorer OS. Conclusions: Allogeneic stem cell transplantation is a valid treatment option for patients with CMML, and its outcome has improved with YOT > 2004. Splenomegaly seems to be a negative factor of OS and EFS in this series. [less ▲]Detailed reference viewed: 2 (0 ULg)
Diffuse xanthomatosis as a presenting feature of multiple myeloma.
; ; et al
in European Journal of Haematology (2010), 84Detailed reference viewed: 15 (3 ULg)
Multiple Myeloma, an update on diagnosis and treatment.
Caers, Jo ; ; et al
in European Journal of Haematology (2008), 81(5), 329-343Detailed reference viewed: 7 (3 ULg)
Limited usefulness of CA125 measurement in the management of Hodgkin's and non-Hodgkin's lymphoma.
Bonnet, Christophe ; Beguin, Yves ; Fassotte, Marie-France et al
in European Journal of Haematology (2007), 78(5), 399-404
BACKGROUND: Several papers have reported an association of high CA125 serum levels with advanced non-Hodgkin's lymphoma (NHL) as well as a relationship between high CA125 values and poor outcome. PATIENTS ... [more ▼]
BACKGROUND: Several papers have reported an association of high CA125 serum levels with advanced non-Hodgkin's lymphoma (NHL) as well as a relationship between high CA125 values and poor outcome. PATIENTS AND METHODS: Ninety-nine patients with NHL or Hodgkin's disease (HD) underwent serum CA125 assessment at diagnosis. Gender, age, presence of B symptoms, performance status (PS), histology, sites of tumor involvement, presence of effusion, clinical stage, age-adjusted International Prognostic Index, C-reactive protein (CRP), Hb, lactate deshydrogenase (LDH) and beta2-microglobulin were evaluated for their association with serum CA125 levels. The impact of CA125 levels and other features on overall (OS) and progression-free (PFS) survival was also assessed. RESULTS: CA125 serum levels were elevated in 34% of the patients, including 19% of patients with aggressive NHL, 45% of patients with indolent NHL, and 29% of patients with HD. Univariate analyses showed that CA125 levels correlated with poor PS, the presence of B symptoms, advanced clinical stage, abdominal, bone marrow or mediastinal involvement, presence of effusions, high aaIPI, low Hb levels and high CRP, LDH or beta2-microglobulin levels. In multivariate analysis, bone marrow involvement, the presence of effusions, and high aaIPI were all associated with high CA125 serum levels. In univariate analyses, OS and PFS were affected by age (PFS only), poor PS, B symptoms, advanced clinical stage, bone marrow or abdominal involvement (PFS only), high aaIPI, low Hb, high CRP or beta2-microglobulin levels. OS and PFS were not different in patients with normal or elevated CA125 levels. Multivariate analyses showed significantly inferior OS and PFS in patients with high beta2-microglobulin but no influence of CA125. CONCLUSION: While CA125 serum level correlates significantly with a number of features associated with more aggressive disease, it does not enhance the performance of standard prognostic markers in the management of patients with NHL or HD. [less ▲]Detailed reference viewed: 69 (6 ULg)
Establishment and characterisation of two novel human KSHV- and EBV-negative Burkitt cell lines, GAL-01 and GAL-02, from a primary lymphomatous effusion
Thielen, Caroline ; Herens, Christian ; Fassotte, Marie-France et al
in European Journal of Haematology (2006), 77(4), 318-326
Objectives: Burkitt's lymphoma (BL) is a highly aggressive mature B-cell neoplasm comprising endemic, sporadic and immunodeficiency-associated variants. Human cell lines constitute a very useful tool to ... [more ▼]
Objectives: Burkitt's lymphoma (BL) is a highly aggressive mature B-cell neoplasm comprising endemic, sporadic and immunodeficiency-associated variants. Human cell lines constitute a very useful tool to investigate the biology of lymphoid neoplasia. In this study, we succeeded in establishing two human cell lines, GAL-01 and GAL-02, from a HIV-negative patient with Epstein-Barr virus (EBV) -negative sporadic BL presenting as an effusion. GAL-01 and GAL-02 were established at diagnosis and after one course of polychemotherapy, respectively. The in vivo effusion occurred in a very peculiar clinical setting; the patient having a previous history of intestinal diffuse large B-cell lymphoma. Methods: The morphologic, immunophenotypic and molecular genetic features of GAL cell lines are reported and compared with those of the parental tumour. The findings clearly demonstrated that the Burkitt effusion did not represent disease progression of the intestinal tumour, but represented a second primary haematological malignancy. The in vivo tumorigenic properties of the cells were tested by subcutaneous injection to NOD/SCID mice. Results: Both cell lines were composed of medium-sized lymphoid cells with clumped chromatin, multiple medium-sized nucleoli and moderate amounts of vacuolated cytoplasm. GAL cells display the phenotype and genotype of a B-cell lineage (positive for CD20, CD79a and clonal rearrangement of Ig heavy chain), carry the c-MYC rearrangement by t(8;22)(q24;q11) translocation and are characterised by the expression of the germinal centre-associated antigens CD10, BCL6, CD38 and absent to low BCL2 expression. EBV and HHV8 were not identified within parental tumour or in cultured cells. Subcutaneous injection of both cell lines to NOD/SCID mice induced tumour formation. Conclusions: GAL-01 and GAL-02, two novel EBV-negative human BL cell lines represent a potentially useful experimental model to study the biology of BL possibly including the resistance to chemotherapy. [less ▲]Detailed reference viewed: 55 (7 ULg)
Role of stromal-derived factor-1 in the hematopoietic-supporting activity of human mesenchymal stem cells.
; Beguin, Yves ; Gothot, André
in European Journal of Haematology (2006), 76(6), 488-93
Mesenchymal stem cells (MSC) have the ability to support and maintain hematopoiesis in vitro. However, mechanisms implicated in this support are not fully characterized. In the present study, the role of ... [more ▼]
Mesenchymal stem cells (MSC) have the ability to support and maintain hematopoiesis in vitro. However, mechanisms implicated in this support are not fully characterized. In the present study, the role of stromal-derived factor-1 (SDF-1)/CXCR4 axis in the interactions between MSC and hematopoietic stem/progenitor cells (HSPC) was studied. Human bone marrow MSC were plated as feeder layers in Dexter-type long-term cultures (LTC) with human cord blood CD34(+) HSPC. Cultures were supplemented weekly with neutralizing antibodies against CXCR4 or SDF-1 for 5 wk. LTC-initiating cell (IC) activity was strongly dependent on the SDF-1/CXCR4 axis, as both antibodies significantly decreased secondary colony-forming cell production. To assess the effect of SDF-1/CXCR4 axis on progenitor cell proliferation, LTC-IC killing assays were carried out: in LTC of CD34(+) cells in contact with MSC, treatment with anti-CXCR4 antibody significantly reduced the number of cycling progenitors. These results indicate that the SDF-1/CXCR4 axis promotes HSPC proliferation in contact with MSC. Interestingly, when HSPC were separated from MSC by a semipermeable membrane, LTC-IC activity became CXCR4 independent. Multiplex analysis of MSC-conditioned medium revealed that in addition to SDF-1, MSC produced stimulatory and inhibitory factors, such as interleukin (IL)-6, IL-11, granulocyte macrophage-colony stimulating factor as well as monocyte-chemoattractant protein-1. Altogether, human MSC support hematopoiesis in Dexter-type cultures through the activation of the SDF-1/CXCR4 axis. Our data further suggest that SDF-1 stimulates retention of HSPC in MSC niches which expose them to stimulatory and inhibitory factors in a paracrine manner. [less ▲]Detailed reference viewed: 42 (5 ULg)
Infections after CD34-selected or unmanipulated autologous hematopoietic stem cell transplantation.
Frere, Pascale ; Pereira-Martins, Maguy ; Fillet, Georges et al
in European Journal of Haematology (2006), 76(2), 102-8
Immune reconstitution may be delayed after CD34-selected compared with unmanipulated autologous peripheral blood stem cell transplantation (PBSCT), resulting in a theoretically increased risk of ... [more ▼]
Immune reconstitution may be delayed after CD34-selected compared with unmanipulated autologous peripheral blood stem cell transplantation (PBSCT), resulting in a theoretically increased risk of infections. In a case-control matched study we compared the incidence of infection in 25 recipients of CD34-selected PBSC (CD34 group) and 75 recipients of unmanipulated PBSC (PBSC group) transplants. The population included 52 males and 48 females suffering from non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 8), multiple myeloma (n = 40) or breast cancer (n = 20). Neutrophil engraftment was comparable in the two groups. The actuarial incidence of infection was similar in the two groups (56% vs. 49% at day 30, and 70% vs. 64% at 1 yr respectively). The proportion of patients with 1, 2 or 3 infections, the number of infectious event per patient (1.32 vs. 1.04; NS), the number of infections before day 15 or 30, between days 31 and 100 or after day 100, the risk of varicella-zoster virus or cytomegalovirus infection or disease, or the use of antibiotic or antifungal therapy, were not increased in the CD34 compared with the PBSC group. The main agents responsible for infection were bacteria, particularly gram-positive cocci, in both groups. Bacteremia accounted for 33% of all infectious events in the CD34 group vs. 16% in the PBSC group (P < 0.05). Fungal infections were rare. In conclusion, our results do not support the notion that CD34-selection of the graft is associated with an increased rate of infection after autologous PBSC transplantation. The role of extended infection prophylaxis should be evaluated. [less ▲]Detailed reference viewed: 18 (3 ULg)
Effect of recombinant human erythropoietin on platelets in patients with anemia of renal failure: correlation of platelet count with erythropoietic activity and iron parameters.
Beguin, Yves ; ; R'Zik, Samir et al
in European Journal of Haematology (1994), 53(5), 265-70
We examined the effect of treatment with rHuEpo on platelet counts in 61 hemodialysis patients and correlated them with changes in erythropoietic activity, iron status and inflammation. Platelets (10(9)/1 ... [more ▼]
We examined the effect of treatment with rHuEpo on platelet counts in 61 hemodialysis patients and correlated them with changes in erythropoietic activity, iron status and inflammation. Platelets (10(9)/1) increased from 220 +/- 80 to 245 +/- 102 after 14 days and stabilized at that level up to day 90 (p < 0.0001). The increment was similar in complete or partial responders but was not observed in failures. Serum transferrin receptor (sTfR, a measure of total erythropoiesis) and Het rose much more progressively, but relative platelet increments correlated with relative increases in sTfR and Hct. Relative platelet increments correlated inversely with relative changes of SeFe or transferrin saturation, but not with their absolute values, nor with baseline ferritin or its progressive decrease. Although baseline platelet count was 12% higher in patients with inflammation and correlated with serum haptoglobin, relative increases were similar in patients with or without inflammation. In conclusion, rHuEpo produced a clinically minor but consistent elevation of platelet counts. These modifications were not related primarily to modifications in iron stores, functional iron deficiency, or inflammation, but paralleled the expansion of erythropoietic activity. The results suggest that rHuEpo has a small positive effect on platelet production, but it cannot be ruled out that this could be partially mediated through functional iron deficiency. [less ▲]Detailed reference viewed: 12 (2 ULg)