Biomedical subjects

A Sonet

Publications and source records attributed to A Sonet.

8 recordsLinked to original sources

PubMed2001

Unusual growth within a meningioma (leukemic infiltrate).

Intracranial meningiomas are generally slow-growing neoplasms. Symptoms depend on their critical intracranial location. The authors describe a case of rapidly enlarging meningioma that became symptomatic as a result of invasion by leukemic cells at the time of a blastic crisis in the context of chronic myeloid leukemia. Infiltration of an intracranial meningioma by cells from extracranial malignant neoplasms is a rare event. Even though central nervous system (CNS) or meningeal involvement is common in some hematologic malignancies, this is, to the best of our knowledge, the first report of invasion of an intracranial meningioma by leukemic cells.

Aged↗

PubMed2000

Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: a GELA study on 974 patients. Groupe d'Etudes des Lymphomes de l'Adulte.

BACKGROUND: Incidence of central nervous system (CNS) recurrence in patients with aggressive non-Hodgkin's lymphoma who did not receive meningeal prophylaxis is about 5%. Controversy remains regarding risk factors associated with such an event preventing a rational approach of prophylactic strategies. PATIENTS AND METHODS: We analyzed a cohort of 974 patients with aggressive lymphoma in complete remission (CR). All the patients received a CNS prophylaxis consisting of intrathecal injections and intravenous high-dose methotrexate. The risk repartition on the basis of the international prognostic index (IPI) of these 974 CR-patients was low (L): 41%, low-intermediate (LI): 27%, high-intermediate (HI): 19%, high (H): 13%. RESULTS: The incidence of isolated CNS relapse was 1.6%. In a first multivariate logistic regression analysis an increased LDH (P = 0.05, RR = 5) and the presence of more than one extranodal site (P = 0.05, RR = 3) were identified as independent risk factors for isolated CNS relapse. Another multivariate analysis incorporating IPI as a unique parameter showed that only IPI remained significantly associated with a higher risk of CNS relapse (L-LI: 0.6% vs. HI H: 4.1%, P = 0.002; RR = 7). CONCLUSION: Prophylaxis notably reduces the risk of CNS recurrence in the higher risk patients. By contrast, we propose the deletion of prophylactic intrathecal injections in the lower risk patients.

Antimetabolites, Antineoplastic↗

PubMed2000

Phase I/II study of 2-chloro-2'-deoxyadenosine with cyclophosphamide in patients with pretreated B cell chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma.

Because of their substantial in vitro synergy, we conducted a dose-escalation study of cyclophosphamide (CP) added to 2-chloro-2'-deoxyadenosine (CdA) in patients with previously treated chronic lymphocytic leukemia and non-Hodgkin's lymphoma. CdA was given at a fixed dose (5.6 mg/m2/day) as a 2-h intravenous (i.v.) infusion, immediately followed by a 1-h i.v. infusion of CP, for 3 days. The initial daily CP dose was 200 mg/m2, and was escalated by 100 mg/m2 increments in successive cohorts of three to six patients to determine the maximum-tolerated dose (MTD). Additional patients were included at the MTD to extend toxicity and response analysis. Twenty-six patients received 68 cycles of chemotherapy. The MTD of CP after CdA 5.6 mg/m2, was 300 mg/m2. Acute neutropenia was the dose-limiting toxicity of this regimen, which was otherwise well tolerated. Delivery of repeated cycles was not feasible in eight patients (31%) because of prolonged thrombocytopenia. Severe infections were seen in three of 68 cycles (4%). The overall response rate was 58% (15 of 26; 95% CI, 36-76%), with 15% complete responses and 42% partial responses. These data show the feasibility of the association of CdA with CP. Given the response rate observed, further studies of this regimen are warranted in untreated patients, in particular with chronic lymphocytic leukemia and with Waldenström macroglobulinemia.

Adult↗

PubMed1999

Toxicities after peripheral blood progenitor cell transplantation for lymphoid malignancies: analysis of 300 cases in a single institution.

Two hundred and seventy-seven consecutive patients with non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27) and multiple myeloma (n = 43) were intensified from October 1989 until April 1997 and received unmanipulated PBPC transplants. Twenty-three patients received a double intensification, out of a total of 300 PBPC transplantations analyzed. Conditioning regimens consisted of total body irradiation (TBI)-containing regimens (n = 141), BEAM (n = 104), high-dose melphalan (n = 26), ICE (n = 23) or other regimens (n = 6). Eighty-four percent of the patients (119/142) evaluable for long-term hematological reconstitution beyond 180 days achieved normal trilineage blood counts. Abnormal hematological parameters were associated with low numbers of CD34+ cells re-infused and with prior exposure to fludarabine. The 100-day and long-term treatment-related mortality rates were 4% and 4%, respectively. Late complications and treatment-related toxicities were influenced by disease history, use of TBI and exposure to fludarabine. Patients older than 60 years did not have greater toxicities or more frequent treatment-related deaths. This analysis suggests that while leading to a limited morbidity and a low mortality rate, intensive chemotherapy with PBPC transplantation still remains a procedure leading to significant short- and long-term toxicities. Better recognition of the risk factors associated with these complications might allow a further decrease in their incidence.

Adolescent↗

PubMed1998

High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral blood progenitor cell transplantation.

Optimal numbers of CD34(+) cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34(+) cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 x 10(9)/L) and unsustained platelet recovery (>50 x 10(9)/L) were analyzed in three groups defined by the number of CD34(+) cells reinfused: a low group with less than or equal to 2.5 x 10(6) CD34(+) cells/kg, a high group with greater than 15 x 10(6) CD34(+) cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P < .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34(+) cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 x 10(6) CD34(+) cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.

Adolescent↗

PubMed1996

Acute leukaemia in paroxysmal nocturnal haemoglobinuria. Case report and review of the literature.

Paroxysmal nocturnal haemoglobinuria (PNH) terminating in acute leukaemia (AL) is an infrequent condition. In several cases, flow cytometric analysis of glycosylphosphatidylinositol anchored membrane proteins such as DAF and CD59/MACIF has suggested the leukaemic cells to be derived from the PNH clone, thereby implicating PNH as a potential preleukaemic disease. In the present paper, we review the data for one patient treated in our hospital and 20 cases reported in the literature from 1969 to 1993. The sex ratio is 1 female/2 males, mean age at diagnosis of PNH was 46 years and the mean interval between the diagnoses of PNH and AL was 53 months. AL type was AML M6 in 8 patients, other types of AML in 12 and ALL in one, with a mean survival of 7.1 months following diagnosis of AL. In all cases analyzed, the PNH phenotype of erythrocytes disappeared with progression of AL, whereas reappearance of this phenotype with complete remission of AL was inconstant. PNH would thus appear to be a potential preleukemic disease. When this disorder terminates in AL, the type is often AML M6, although ALL is also possible. The prognosis of AL in PNH is poor as for other secondary leukaemias. Apart from marrow aplasia, leukaemic transformation is another life threatening complication of PNH which may justify allogeneic bone marrow transplantation (allo-BMT) and potential leukaemic transformation can therefore be an additional argument in favour of allo-BMT when pancytopenia develops in PNH patients.

Acute Disease↗

PubMed1995

Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma.

Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment-related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Nonfollicular small B-cell lymphomas: a heterogeneous group of patients with distinct clinical features and outcome.

Two hundred sixteen patients with a nonfollicular small cell lymphoma followed up in our department over a 5-year period have been reviewed to define the clinical behavior and survival of patients with each histologic subtype. The respective frequencies of major subtypes were: small lymphocytic/lymphoplasmacytoid lymphoma (immunocytoma, SL/LPL), 28%; large cell-rich immunocytoma (LCRI), 7%; mantle cell lymphoma (MCL), 24%; mucosa-associated lymphoid tissue-lymphoma (MALT-L), 20%; other rare subtypes, 6%; and nonclassified or nonreviewed, 14%. The SL/LPL patients and the MALT-L patients had a relatively indolent disease, usually disseminated for SL/LPL and usually localized for MALT-L. Both subtypes have a long time to treatment failure (TTF; median, 48 and 58 months, respectively) and long survival (median, 118 and 98 months, respectively). The LCRI patients or the MCL patients had more aggressive clinical or biologic features and experienced shorter TTF (median, 26 and 14 months, respectively) and shorter survival (median, 55 and 52 months, respectively). None of these histologic subtypes was associated with a significant cure rate. MALT-L patients did relapse regardless of the initial localization or treatment and at a similar rate to the SL/LPL patients. Factors associated with a worse outcome in nonfollicular small cell lymphoma patients are identical to those described in other lymphoma subtypes: advanced clinical stage, poor performance status, high tumor bulk, and high lactic dehydrogenase or beta 2microglobulin levels. For patients with disseminated disease, standard chemotherapy regimens did not allow a long TTF; therefore, new therapeutic strategies must be developed.

Adult↗