ANALYSE DES RECHUTES DANS LES LMNH LOCALISES AGRESSIFS TRAITES PAR LES PROTOCOLES GOELAMS 02 ET 03

AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Polyradiculonévrite de type Guillain-Barré au cours d'une Maladie de Waldenström (rôle aggravant de la Fludarabine ?)

La macroglobulinémie de Waldenström (MW) est une hémopathie maligne rare, puisqu'elle atteint seulement 0,5 personne sur 100.000 par an, préférentiellement des hommes âgés de plus de 60 ans. Le syndrome de Guillain-Barré (SGB) est une maladie également peu commune (incidence: 1,5 cas/ 100.000). Nous avons la chance de pouvoir étudier ici ces deux pathologies, à travers le cas d'une patiente porteuse depuis l'age de 55 ans de la MW, qui a développé au bout de 7 ans d'évolution un SGB. Nous nous sommes efforcés de définir à travers cette étude quels pouvaient être les facteurs déclenchants voire aggravants de cette pathologie, et il nous a semblé que seule la cause médicamenteuse devait être retenue. Il nous est difficile d'établir la responsabilité de la Fludarabine seule dans l'apparition du SGB, la littérature est en effet pauvre en exemples de ce type. Cependant, le délai d'apparition et la lymphopénie constatés permettent de penser qu'il existerait bien une action neurotoxique périphérique de la Fludarabine à dose usuelle, quel que soit le type de pathologie pour lequel elle est utilisée. Le statut immunitaire du patient, en particulier la baisse du taux de CD4+, semble lié à l'apparition du SGB. Nous avons d'autre part constaté que certains malades atteints d'un SGB avaient bénéficié d'une prise de TMP-SMX concomitante à l'administration de Fludarabine, tout comme la patiente de notre observation. Cet élément ne nous permet donc pas d'exclure la possibilité d'une action neurotoxique du TMP-SMX, produit dont l'utilisation est très répandue, bien que la littérature dispose à ce sujet de peu d'exemples. Une dernière hypothèse de travail nous semble envisageable au terme de cette étude : il est en effet possible qu'une toxicité neurologique résulte de l'association du TMP-SMX et de la FludarabineAMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation of residual disease in b-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements

We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19 + cells were >25% and the ratio of CD5 + CD19 + /CD19 + cells was >25% According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B-lineage acute lymphoblastic leukemia cells.

International audienceACKGROUND AND OBJECTIVES: Zeta-associated protein 70 (ZAP-70), a member of the Syk family of protein tyrosine kinases, is normally expressed in T and NK cells. While little is known about ZAP-70 expression in normal human B cells, it has been reported that ZAP-70 is expressed in a subset of patients with chronic lymphocytic leukemia (CLL) with a poor prognosis. In this study, we examined the expression and phosphorylation status of ZAP-70 in B-lineage acute lymphoblastic leukemia (Blin-ALL).DESIGN AND METHODS: First, ZAP-70 protein expression was assessed by Western blotting and flow cytometry and ZAP-70 mRNA transcripts were analyzed by reverse transcription polymerase chain reaction (RT-PCR) on human precursor B cell lines. Experiments were then carried out on cells obtained from 18 patients with Blin-ALL and from normal human bone marrow.RESULTS: ZAP-70 was constitutively expressed and phosphorylated on tyr319 in human precursor Blin-ALL cell lines as well as in primary B leukemic cells from all examined Blin-ALL patients with pro-B, pre-B and B phenotypes, but not in malignant myeloid cells. Importantly, analysis of normal human bone marrow revealed expression of ZAP-70 transcripts only in the CD34+ cell fraction (either CD19-CD10- or CD19+CD10+) but not in the CD34- cell fraction (CD19+sIgM- pre-B cells or CD19+sIgM+ immature B cells).INTERPRETATION AND CONCLUSIONS: ZAP-70 was found to be expressed in the CD34+ normal bone marrow compartment including earlier B-cell progenitors, but not in CD34- pre-B and immature B cells. By contrast, ZAP-70 was consistently expressed and phosphorylated in Blin-ALL cells. Further studies are required to determine whether ZAP-70 may play a pathophysiological role in Blin-ALL.

Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95

International audiencePeripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear as highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite non satisfactory results with the CHOP regimen, it remains the reference front line therapy in these diseases, but has not been challenged in phase III trials. The GOELAMS group devised an alternative therapeutic schedule including Etoposide, Ifosfamide, Cisplatin alternating with Doxorubicin, Bleomycin, Vinblastin, Dacarbazine (VIP-reinforced-ABVD) and compared it to CHOP/21 as front-line treatment in non cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-years event-free survival (EFS) rate. Secondary objectives were to compare the response rates, overall survival, and toxicities as well as identify prognostic factors. 88 patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-years EFS. ALCL type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. The VIP-rABVD regimen was not superior to CHOP/21 in term of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference arm in these lymphomas

High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years.

International audienceAutologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P = .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the per-formance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia, P = .01). The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL. This trial has been registered with ClinicalTrials.gov under identifier NCT00696735