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A Delannoy

Publications and source records attributed to A Delannoy.

At least 37 records · Page 2Linked to original sources
PubMed1997

Age-adapted induction treatment of acute lymphoblastic leukemia in the elderly and assessment of maintenance with interferon combined with chemotherapy. A multicentric prospective study in forty patients. French Group for Treatment of Adult Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its poor prognosis. Forty patients with ALL, aged 55 years or older, and with good performance status (ECOG <3) were prospectively treated according to an age-adapted regimen: induction therapy was derived from the LALA87 protocol while the feasibility of treatment with interferon combined with chemotherapy was assessed during maintenance. Compared with younger adults treated according to the LALA87 protocol, elderly patients did not present with more adverse prognostic features, except for a lower incidence of T cell ALL (9 vs 31%, P=0.005). There were even less patients with a high leukocyte count (15 vs 38%, P=0.003), a characteristic associated with adverse prognosis while the incidence of Philadelphia-positive (Ph-positive) ALL was not significantly increased compared to younger adults (31 vs 20%, P=0.2). After completion of induction therapy, with or without salvage treatment, 85% (CI: 70-94%) obtained a complete response (CR) while treatment-related mortality during induction was 7.5% (CI: 2-20%). Median overall survival and disease-free survival were 14.3 months and 14 months, respectively, which, although inferior to results achieved in younger adults, compares favorably with available data in the elderly. Treatment with IFN proved feasible in most patients but had to be discontinued in eight patients because of toxicity. Age-adapted treatment improves the prognosis of ALL in the elderly even if, in most cases, a cure cannot be achieved.

Aged↗
PubMed1997

FISH identifies different types of duplications with 12q13-15 as the commonly involved segment in B-cell lymphoproliferative malignancies characterized by partial trisomy 12.

Clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data of 18 patients with different subtypes of B-cell non-Hodgkin's lymphoma, cytogenetically characterized by partial trisomy 12, are presented. These chromosomal changes occurred predominantly in clinically progressive chronic lymphocytic leukemia, mixed cell type, and advanced-stage follicle center cell lymphoma at the time of relapse or transformation into diffuse large cell lymphoma. Partial trisomy 12 consistently included the long arm of chromosome 12, either completely or partially, and resulted from dup(12q) or other rearrangements involving chromosome 12. The duplications were cytogenetically identified as dup(12)(q13q23), dup(12)(q13q22), or dup(12)(q13q15) in follicle center cell lymphoma or t(14;18)-positive diffuse large cell lymphoma; dup(12)(q13q22) or dup(12)(q13q24) in chronic lymphocytic leukemia; and dup(12)(q13q21) in a case of t(14;18)-negative diffuse large cell lymphoma. FISH, using library probes and a panel of YAC probes, mapped along the long arm of chromosome 12, confirmed the cytogenetic results in all cases analyzed except for three cases of t(14;18)-positive follicle center lymphoma or diffuse large cell lymphoma with dup(12q). In these cases, FISH showed similar, possibly identical, duplications, which involved a region more centromeric (12q11-21) than assumed by karyotypic analysis (12q13-22 or 12q13-23) and included alphoid DNA sequences, a combination hitherto unknown. In addition, commonly duplicated regions of chromosome 12 could be defined: 12q11-21, including alphoid DNA sequences for follicle center cell lymphoma or t(14;18)-positive diffuse large cell lymphoma, 12q13-22 for chronic lymphocytic leukemia, and 12p13-q15 for marginal zone cell lymphoma, all of which overlapped in 12q13-15. Whether these regions, especially 12q13-15, may contain genes which are important in malignant transformation or disease progression of B-cell lymphoproliferative malignancies characterized by complete or partial trisomy 12 remains to be determined.

Aged↗
PubMed1996

2-chloro-2'-deoxyadenosine: clinical applications in hematology.

The anticancer drug 2-chloro-2'-deoxyadenosine (CdA) belongs to the family of purine nucleoside analogs. CdA is exquisitely cytotoxic both to the dividing and to the non-dividing lymphocyte, which supports its use in lymphoproliferative disorders of low-grade malignancy. Indeed, the best clinical results with CdA are achieved in hairy-cell leukemia, in chronic lymphocytic leukemia, in Waldenström's macroglobulinemia and in low-grade malignant lymphoma. Most patients with hairy-cell leukemia achieve a complete response with a single course of CdA. However, the disease is not eradicated and a fraction of complete responders will eventually relapse. In chronic lymphocytic leukemia and in malignant lymphoma, complete or partial responses can be achieved in approximately 40% of previously treated patients, even after classical chemotherapy has failed. However, few responses sustain beyond 1 to 2 years, while longer unmaintained responses may be obtained in Waldenström's macroglobulinemia. More responses (70-80%) are achieved in patients with chronic lymphoproliferative disorders treated de novo with CdA but their impact on survival remains to be established. More than 10 years after its first use in clinical practice, late adverse consequences of the severe and sustained immunosuppression induced by CdA have not been reported but should still be closely monitored.

2-Chloroadenosine↗
PubMed1996

Infectious complications after 2-chlorodeoxyadenosine therapy.

Infection is a common adverse event after therapy with nucleoside analogs, including 2-chlorodeoxyadenosine (CdA). However, the incidence of CdA-related infections has been poorly documented. In this study we compare, in the same patient population, the incidence of infectious episodes during the 6-month period before CdA to their incidence during the 6 months after initiating therapy. Ninety-five patients with hematological malignancies were studied. The incidence of infectious episodes almost doubled after CdA (0.87 vs. 0.47 during the pre-CdA period). The following factors were associated with an increased risk of infection after therapy: a history of previous chemotherapy, infection during the pre-CdA period and a diagnosis of chronic lymphocytic leukemia or of non-Hodgkin's lymphoma. Age, neutrophil and lymphocyte count at onset of CdA and time interval between diagnosis and therapy with CdA did not correlate with the infectious risk. The pattern of infections was modified after therapy with an increase of herpes virus infections ( 1 vs. 8 episodes, p=0.04) and of fever of unknown origin (6 vs. 17 episodes, p=0.03). In conclusion, a population at high risk for developing infectious complications after CdA therapy can be identified. Specific measures aimed at reducing the incidence of infectious events should concentrate on this population.

Adult↗
PubMed1996

Limited activity of mini-dose interferon alpha-2a in the treatment of myelodysplastic syndrome.

Impairment in marrow function often characterizes the evolution of myelodysplastic syndrome. As a differentiating agent, interferon alpha 2a (INF alpha) has been shown to be active in the correction of cytopenias related to myelodysplastic syndromes (MDS). We report the clinical course of 9 patients with MDS treated with low-dose subcutaneous INF alpha (1 x 10(6), 3 times per week). A significant effect on anemia was only demonstrated in one patient (11%). In the other, eight, therapy was totally ineffective and four of them could not receive the complete treatment due to worsening cytopenias or leukemic transformation. In conclusion, in our study, INF alpha had only limited activity in the treatment of myelodysplastic syndrome.

Drug Evaluation↗
PubMed1996

Clinical evidence for an engraftment syndrome associated with early and steep neutrophil recovery after autologous blood stem cell transplantation.

Seventy autologous peripheral blood stem cell transplants (APBSCT) performed in 61 cancer patients were retrospectively analyzed. Patients were heterogenous with regard to malignancy, conditioning regimens and use of growth factors after transplantation. Six patients developed a non-infectious fever, fluid retention and pulmonary interstitial infiltrates during the early phase of neutrophil recovery. Diarrhea was observed in four of these patients and cutaneous rash in three. The clinical condition improved spontaneously in one patient, and within 48 h after steroid therapy in four. One patient died from multiple organ failure. Age, sex (all patients were female; P = 0.07), and time to platelet recovery did not distinguish the six courses complicated by the hypothetical engraftment syndrome (ES) from the other 64 courses taken as controls. However, neutrophil recovery > 0.5 x 10(9)/l occurred earlier (P = 0.01), and the neutrophil count increment during the early phase of recovery was steeper in ES patients (P = 0.003). ES was also associated with infusion of a high number of CD34+ progenitors (P = 0.03) and conditioning with busulfan (P = 0.03). Although all ES patients received G-CSF after transplantation, an association of ES with G-CSF use could not be demonstrated, possibly because of the small number of courses not supported by G-CSF. However, in one patient, ES did not recur after a second transplant unsupported by growth factors. Our study supports the idea of an engraftment syndrome associated with an early and steep neutrophil recovery after APBSCT.

Adult↗
PubMed1995

Progressive mediastinal widening after therapy for Hodgkin's disease.

A residual mass after treatment of Hodgkin's disease points to the diagnosis of fibrotic residue or of persistent disease. Radiological and radionuclide imaging, although helpful, cannot differentiate between both conditions with absolute certainty. Thus, residual masses are followed up: stable or regressive masses strengthen the hypothesis of fibrotic residue, while enlarging masses evoke relapsing disease. We report on a patient with an enlarging residual mass after completion of therapy, which proved to be a benign thymic hyperplasia after histological analysis. Previously reported similar observations are reviewed.

Adult↗
PubMed1995

Trisomy 3 is a consistent chromosome change in malignant lymphoproliferative disorders preceded by cold agglutinin disease.

Cold-antibody autoimmune haemolytic anaemia is a rare entity that has been associated with a wide variety of pathological processes, including malignant lymphoproliferative disorders. In this retrospective study we recorded, as far as possible, clinical, haematological, immunological, morphological, pathological, cytogenetic and molecular data on 10 patients with cold agglutinin disease (CAD). Cytogenetic anomalies were found in four cases in which an underlying lymphoma could be evidenced. Trisomy 3 was the only recurrent aberration in our series. It was observed in all patients with abnormal karyotype, either as a complete trisomy or as a partial trisomy of the long arm. The importance of this particular karyotypic aberration in the monitoring of CAD is emphasized.

Anemia, Hemolytic, Autoimmune↗
PubMed1995

Cyclosporin A in the treatment of refractory B chronic lymphocytic leukemia (B-CLL).

Partial tumoral responses have been described after cyclosporin A treatment in refractory B-chronic lymphocytic leukemia patients. We report the effect of this therapy in five patients prospectively treated with oral conventional dose of cyclosporin A. Antitumoral efficiency was marginal (one sustained partial response among five patients) which, added to a potential worsening of natural and therapy-related immunodepression, limits its use in this instance.

Adult↗
PubMed1995

2-Chlorodeoxyadenosine (CdA) for patients with previously untreated chronic lymphocytic leukemia (CLL).

The encouraging therapeutic results attained with the purine analogue CdA in patients with previously treated CLL prompted us to assess its potential in untreated CLL patients. Nineteen patients, 13 males and six females, median age 65 years (range 27-75), with previously untreated CLL were given monthly courses of CdA, 0.12 mg/kg/day as 2-h i.v. infusions for 5 days, until maximum response or excessive toxicity. Five patients with Binet's stage A, 10 with stage B and four with stage C CLL entered the study. After a median of five courses of CdA (range 1-9) nine complete responses (CR = 47%, CI: 24-69%), five partial responses (PR = 26%, CI: 7-46%) and five failures (= 26%, CI: 7-46%) were recorded. In five complete responders and in one partial responder cytofluorometric analysis of blood and/or bone marrow failed to demonstrate a residual clonal B cell population. A search for residual disease by PCR technology and by immunostaining of bone marrow biopsies however disclosed residual leukemic cells in these six cases. Adverse reactions included fever of unknown origin (n = 3), pneumonia (n = 2), herpes simplex infection, herpes zoster, an anal abscess, a cutaneous rash, autoimmune hemolysis and mental disturbance (one patient each). In this small cohort, neither age, stage, blood counts, cytogenetics or pattern of bone marrow infiltration at inclusion were predictive for response. From these preliminary data, we conclude that CdA has remarkable short-term efficacy in patients with previously untreated CLL. However, toxicity is not negligible and long-term benefit from therapy with CdA still has to be established.

Adult↗
PubMed1995

Karyotype in acute myeloblastic leukemia: prognostic significance in a prospective study assessing bone marrow transplantation in first remission.

To evaluate the prognostic value of the karyotype in acute myeloblastic leukemia when patients are allocated to have either autologous bone marrow transplantation (BMT) or allogeneic BMT at the time of first remission (CR1), we have prospectively followed 134 consecutive patients from diagnosis. CR was achieved in 118 patients. Allogeneic BMT and autologous BMT were performed in 25 and 43 CR1 patients, respectively. Applying the karyotype classification of Keating et al for remission duration (favorable: t(15;17), inv(16); intermediate: normal, X -Y, t(8;21); unfavorable: other abnormalities), 10 patients had a favorable, 49 an intermediate, and 44 an unfavorable karyotype. The 5-year leukemia-free survival (LFS) probabilities for patients with a good, intermediate and unfavorable karyotype were 65%, 32% and 11%, respectively (log rank test P = 0.0019). The probabilities of relapse were 35% in patients with a favorable karyotype, 52% with an intermediate karyotype and 87% with an unfavorable karyotype (P = 0.0004). In the patients who had autologous BMT in CR1, the LFSs were 100%, 33% and 10% with favorable, intermediate and unfavorable karyotype, respectively (P = 0.04). The karyotype was of no prognostic value in patients receiving allogeneic BMT who had BMT in CR1. This study shows that the karyotype retains its prognostic value when the intentions is to treat patients with acute myeloblastic leukemia in CR1 with BMT. Autologous BMT was not able to improve the poor prognosis associated with an unfavorable karyotype.

Adolescent↗
PubMed1994

Aggressive lymphomas with renal involvement: a study of 48 patients treated with the LNH-84 and LNH-87 regimens. Groupe d'Etude des Lymphomes de l'Adulte.

In order to describe renal involvement in aggressive non-Hodgkin's lymphomas (NHLs) and its prognostic significance, we reviewed the outcome of 48 patients with renal involvement treated with the LNH-84 or LNH-87 regimen. Histology was diffuse large cell in 29 (60%) patients; immunoblastic, diffuse mixed cell and lymphoblastic in four each; follicular large cell, diffuse small cleaved cell and diffuse small non-cleaved cell in one each; and unclassified in four. Ann Arbor stage was IV in 44 patients, and IE or IIE in four. Tumour mass > or = 10 cm, performance status (ECOG scale) > 2 and increased LDH level were present in 69%, 20% and 76% of patients respectively. Fifteen patients (31%) had multiple intraparenchymal nodules, 14 (29%) had direct spread into the kidney from a perirenal mass, ten (21%) had a single intraparenchymal nodule and nine (19%) had diffuse infiltration. Twenty-one patients (43%) presented with bilateral lesions. Three patients (6%) presented with acute renal failure. Ten other patients (21%) had serum creatinine > 120 mumol l-1. In 12 of these 13 patients renal function was restored with chemotherapy. Twenty-eight patients (57%) achieved complete remission. Estimated 4 year disease-free survival was 39%. Disease-free survival and actuarial survival at 4 years were estimated to be 58% respectively. Two renal parameters had adverse prognostic significance for survival: renal hilum involvement (P = 0.02) and diffuse renal infiltration (P = 0.01). A Cox model identified only two independent prognostic factors for survival, namely performance status > or = 2 and tumour size > or = 10 cm. We conclude that alteration in renal function occurs in 27% of patients with renal involvement. Systemic chemotherapy improves renal function rapidly. Long-term outcome is similar to that expected in NHL patients presenting with the same prognostic factors.

Actuarial Analysis↗
PubMed1994

A single course of 2-chloro-deoxyadenosine does not eradicate leukemic cells in hairy cell leukemia patients in complete remission.

The nucleoside analog 2-chlorodeoxyadenosine (2-CdA) has recently emerged as a most promising treatment for hair-cell leukemia (HCL). The response rates are high regardless of prior therapy, and the duration of complete responses (CR) after a single course of treatment is longer than with any other therapeutic agent. We investigated the presence of minimal residual disease (MRD) in ten HCL patients treated in our institution with 2-CdA. The presence of residual leukemic cells was investigated in patients in CR following one course of treatment, using the polymerase chain reaction (PCR) and heavy-chain immunoglobulin genes (IgH), or TCR delta derived clonospecific probes. Eight patients achieved a complete remission after a single course of treatment, as evaluated at 6 months. Among these patients, seven are still in CR with a median follow-up of 12 months (range, 6-20 months) and one has relapsed after 15 months. Using PCR, all the evaluable patients remaining in CR showed persistent evidence of detectable MRD with no sign of decrease over the observation period. From this small series, we conclude that a single course of 2-CdA does not eradicate HCL and that persistence of residual leukemic cells appears to be common in patients in complete morphologic remission. Whether persistence of MRD will have an impact on long-term outcome, or whether HCL patients in morphologic CR with persistent MRD will remain so, is a matter of longer follow-up.

Aged↗
PubMed1994

2-Chlorodeoxyadenosine therapy in advanced chronic lymphocytic leukaemia.

The therapeutic potential of 2-chlorodeoxyadenosine (CdA) in patients with advanced chronic lymphocytic leukaemia (CLL) remains controversial with response rates in clinical trials ranging from 44 to 67%. This report describes our experience with CdA in 22 CLL patients having already undergone previous treatment. CdA was given by continuous intravenous infusion at a dose of 4 mg/m2/day for 7 days (4 patients) or as 2-h intravenous infusions at a dose of 5.6 mg/m2/day for 5 days (18 patients). Partial (n = 5) or complete (n = 2) response was obtained in 7 cases. As compared to unresponsive patients, responding subjects received CdA earlier in the course of their disease (mean interval between diagnosis and CdA therapy 58 vs 102 months), were less thrombocytopenic at initiation of CdA (mean platelet count 165 x 10(9)/L vs 81 x 10(9)/L) and experienced less severe neutropenia during the first course of therapy (mean minimal neutrophil count 1.55 x 10(9)/L vs 0.43 x 10(9)/L). None of 6 patients with CLL refractory to fludarabine responded to CdA. An evaluation of haematological toxicity during the first course of treatment showed grade 4 neutropenia (< 0.5 x 10(9)/L) in 7 cases and grade 4 thrombocytopenia (< 25 x 10(9)/L) in one of 19 cases where the platelet count was greater than 25 x 10(9)/L at initiation of CdA. In comparison with earlier reports, the present series of patients had received relatively heavy prior therapy, experienced more severe haematological toxicity and demonstrated a lower total response rate.

Aged↗
PubMed1994

2-Chlorodeoxyadenosine therapy in Waldenstrom's macroglobulinaemia.

Despite some encouraging first results, experience with 2-chlorodeoxyadenosine (CdA) in the treatment of Waldenström's macroglobulinaemia (WM) has not as yet been very extensive. The present paper reports a clinical trial of the use of CdA in 18 patients having previously treated (n = 13) or untreated (n = 5) WM. CdA was administered by continuous intravenous infusion at a dose of 4 mg/m2/day for 7 days (5 patients) or as 2-h intravenous infusions at a dose of 5.6 mg/m2/day for 5 days (13 patients). Partial response was obtained in 7 cases. In this small series, no correlation could be found between response to CdA and patient characteristics at inclusion. During the first course of therapy, grade 4 neutropenia (< 0.5 x 10(9)/L) and thrombocytopenia (< 25 x 10(9)/L) developed in respectively 4 and 6 cases. In comparison with earlier reports haematological toxicity was more severe and the overall response rate lower in the present series of patients.

Aged↗