Diffuse large B-cell lymphoma of Waldeyer's ring has distinc clinicopathologic features: a GELA study.

in Annals of Oncology (2012)

Background Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. Patients and methods We analyzed a cohort of 187 primary Waldeyer's ring ... [more ▼]

Background Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. Patients and methods We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. Results Most patients (92%) had stage I–II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03). Conclusions WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart. [less ▲]

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 ▲]

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma : final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

in Haematologica (2010), 95

Co-transplantation of mesenchymal stem cells might mitigate acute GvHD without abrogating graftversus- tumour alloreactivity after allogeneic transplantation with non-myeloablative conditioning

Conference (2009)

Background: Results of nonmyeloablative HCT in pts with HLA-mismatched donors have been disappointing due to high incidence of graft rejection and severe acute GVHD. Recent studies have suggested that ... [more ▼]

Background: Results of nonmyeloablative HCT in pts with HLA-mismatched donors have been disappointing due to high incidence of graft rejection and severe acute GVHD. Recent studies have suggested that infusion of mesenchymal stem cells (MSC) the day of HCT might promote engraftment and prevent acute GVHD after myeloablative allogeneic HCT. However, some studies suggested that MSC co-infusion might abrogate graft-versus-host alloreactivity and graft-versus-tumor effects. This prompted us to investigate whether MSC infusion a few hours before HCT could allow nonmyeloablative HCT from HLA-mismatched donors to be performed safely (i.e. with a 100-day incidence of nonrelapse mortality < 35%). Methods: 20 patients with hematological malignancies were given MSC (1-2 x 10E6 cells/kg) from third party donors a few hours before PBSC from HLA-mismatched unrelated donors, after conditioning with 2 Gy TBI and fl udarabine 90 mg/m. Postgrafting immunosuppression included tacrolimus (day -3 to +180; tapered by day +365) and mycophenolate mofetil (tid days 0 to +42). HLA-compatibility was assessed at the HLA-A, -B, -C, -DRBI and DQBI loci: 13 pairs were mismatched for at least one HLA class I antigen (including 4 pairs who were also mismatched for 1 HLA-class II antigens (n=3) or 1 HLA-class I allele (n=1)), 1 pair was mismatched for 2 HLA class II alleles, while 6 pairs were mismatched for a single HLA class I (n=3) or HLA class II (n=3) alleles. Results: Median follow-up for surviving patients was 288 (range, 76-571) days. One patient with secondary AML had primary graft rejection, while the remaining 19 patients had sustained engraftment. Median donor T-cell chimerism levels on days 28, 100, 180 and 365 after HCT were 90%, 98%, 96%, and 98%, respectively. Grade II, III and IV acute GVHD were seen in 5, 2 and 1 patients, respectively, while 7 experienced NIH moderate/severe chronic GVHD. Three of 7 patients with measurable disease at transplantation achieved complete remission on days 41, 104 and 353 after HCT. Two patients died of nonrelapse causes on days 74 and 114 after HCT, while 3 died of disease progression. Projected 1-yr overall and progressionfree survivals were 77% and 61%, respectively. Conclusions: HLA-mismatched nonmyeloablative HCT with MSC co-infusion appeared to be safe, with MSC co-infusion possibly mitigating graft-versus-host alloreactivity without abrogating graft-versus-tumor effects. Survival is encouraging. [less ▲]

Selective defect of anti-pneumococcal IgG in a patient with persistent polyclonal B cell lymphocytosis.

in European Journal of Internal Medicine (2009), 20(3), 62-5

BACKGROUND: Persistent polyclonal B cell lymphocytosis (PPBL) is a rare condition characterized by increased IgM and large excess of B cells with an IgD(+) CD27(+) phenotype. In normal individuals, these ... [more ▼]

BACKGROUND: Persistent polyclonal B cell lymphocytosis (PPBL) is a rare condition characterized by increased IgM and large excess of B cells with an IgD(+) CD27(+) phenotype. In normal individuals, these cells play a central role in the defense against pneumococcal infection. So far, few studies have characterized humoral immune responses in PPBL patients. We therefore measured IgG directed against S. pneumoniae antigens in a 51 yr-old woman with PPBL before and after vaccination with a pneumococcal 23-valent polysaccharide vaccine. METHODS: Antibodies against pneumococcal antigens were measured first with an overall immunoassay using microplates coated with the 23-valent pneumococcal vaccine. A serotype-specific test was also performed according to the WHO consensus protocol. RESULTS: Despite a large number of IgD(+) CD27(+) cells, our patient had low baseline titers of IgG directed against pneumococcal antigens and did not significantly respond to a 23-valent polysaccharide vaccine against S. pneumoniae. On the contrary, she had good titers of IgG directed against tetanus toxoid. CONCLUSION: IgM(+) IgD(+) CD27(+) cells which accumulate in this patient with typical PPBL patient failed to perform IgG isotype switch after a polysaccharide vaccine. The potential mechanisms and relationships with the main features of PPBL are discussed. Further studies on a larger number of similar patients are needed. [less ▲]

Les anticorps monoclonaux en hématologie en 2009

in Revue Médicale de Liège (2009), 64

Directed against the CD20 antigen on B lymphocytes, rituximab (MabThera) is now incorporated in the first line therapy of symptomatic follicular as well as diffuse large B cell non-Hodgkin's lymphoma and ... [more ▼]

Directed against the CD20 antigen on B lymphocytes, rituximab (MabThera) is now incorporated in the first line therapy of symptomatic follicular as well as diffuse large B cell non-Hodgkin's lymphoma and offers superior response and survival rates. 90Y ibritumomab tiuxetan (Zevalin) combines the specificity of rituximab for the CD20 antigen and the therapeutic effect of β irradiation. Given in monotherapy, it constitutes an interesting alternative therapy for follicular lymphomas in second relapse. Alemtuzumab (MabCampath) recognizes the CD52 antigen and offers encouraging results in chronic lymphocytic leukemia resistant to classical chemotherapy. [less ▲]

Risk adaptive treatment in Hodgkin's lympoma: reduction of radiation dose and irradiated volume

in Belgian Journal of Medical Oncology [=BJMO] (2008), 2(2), 85-97

Treatment–related late complications on nontarget normal tissues and appearance of secondary malignancies are well known side-effects induced by effective treatment regimens currently used in the curative ... [more ▼]

Treatment–related late complications on nontarget normal tissues and appearance of secondary malignancies are well known side-effects induced by effective treatment regimens currently used in the curative approach of early and advanced Hodgkin’s lymphoma. Radiotherapy (RT) and chemotherapy (CT) can lead to these late complications. Efforts have been conducted to reduce the morbidity and mortality related to these treatments. In particular there has been a progressive shift from radiotherapy used as sole modality to chemotherapy as first line followed by consolidation radiotherapy. As the side-effects of radiotherapy are linked to dose, volume and interaction with chemotherapy, trials have been launched to assess the impact of modifying the characteristics of the radiation treatment. For early-stage Hodgkin’s lymphoma radiotherapy cannot be avoided but dose and volume can be reduced. In advanced Hodgkin’s lymphoma omitting radiotherapy seems reasonable only in case of complete response (CR). The clinical trials allowing such a paradigm shift are highlighted in this review. [less ▲]

Comment je traite...La leucémie myéloblastique aiguë (LMA) du sujet age en bon état général.

in Revue Médicale de Liège (2008), 63(2), 59-63

This article describes the treatment of acute myeloid leukemia in older patients with good performance status, and then discusses briefly some future therapeutic perspectives.

CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: A study by the Groupe d'Etude des Lymphomes de I'Adulte

in Journal of Clinical Oncology (2007), 25(7), 787-792

Purpose Chemoradiotherapy has been considered standard treatment for patients with limited-stage aggressive lymphoma on the basis of trials conducted before the introduction of the International ... [more ▼]

Purpose Chemoradiotherapy has been considered standard treatment for patients with limited-stage aggressive lymphoma on the basis of trials conducted before the introduction of the International Prognostic Index. To evaluate this approach in elderly patients with low-risk localized lymphoma, we conducted a trial comparing chemoradiotherapy with chemotherapy alone. Patients and Methods Previously untreated patients older than 60 years with localized stage I or II histologically aggressive lymphoma and no adverse prognostic factors of the International Prognostic Index were randomly assigned to receive either four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus involved-field radiotherapy (299 patients) or chemotherapy alone with four cycles of CHOP (277 patients). Results With a median follow-up time of 7 years, event-free and overall survival did not differ between the two treatment groups (P =.6 and P =.5, respectively). The 5-year estimates of event-free survival were 61% for patients receiving chemotherapy alone and 64% for patients receiving CHOP plus radiotherapy; the 5-year estimates of overall survival were 72% and 68%, respectively. In a multivariate analysis, overall survival was affected by stage II disease (P <.001) and male sex (P =.03). Conclusion In this large prospective study, CHOP plus radiotherapy did not provide any advantage over CHOP alone for the treatment of low-risk localized aggressive lymphoma in elderly patients. [less ▲]

Stem cell transplantation in ALL : a donor versus no donor comparison in the EORTC ALL-4 study

in Leukemia Research (2007)