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1.
Ann Oncol ; 27(5): 902-7, 2016 05.
Article in English | MEDLINE | ID: mdl-26787238

ABSTRACT

BACKGROUND: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. DESIGN: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. RESULTS: The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the ≥1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. CONCLUSION: Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study.


Subject(s)
Drug Resistance, Neoplasm/drug effects , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Thalidomide/analogs & derivatives , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bortezomib/administration & dosage , Bortezomib/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Male , Middle Aged , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/pathology , Thalidomide/administration & dosage , Thalidomide/adverse effects
2.
Br J Dermatol ; 169(3): 579-86, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23646868

ABSTRACT

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease characterized by malignant proliferation of a contingent blastic plasmacytoid dendritic cell. This rare entity is recognized mostly by cutaneous spreading, or not having a leukaemic component. The prognosis is very poor. OBJECTIVES: To study a large cohort of 90 patients with BPDCN, to define additional symptoms to form a correct diagnosis earlier, and to manage such patients accordingly. METHODS: We retrospectively reviewed BPDCN cases registered in the French Study Group on Cutaneous Lymphoma database between November 1995 and January 2012. Ninety patients were studied. Demographic data, clinical presentation, initial staging and outcome were recorded. RESULTS: The group contained 62 male and 28 female patients (sex ratio 2·2). Their ages ranged from 8 to 103 years at the time of diagnosis (mean 67·2 years). Three major different clinical presentations were identified. Sixty-six patients (73%) presented with nodular lesions only, 11 patients (12%) with 'bruise-like' patches and 13 (14%) with disseminated lesions (patches and nodules). Mucosal lesions were seen in five patients (6%). The median survival in patients with BPDCN was 12 months. CONCLUSIONS: We here distinguish three different clinical presentations of BPDCN. A nodular pattern is a more common feature than the originally reported 'bruise-like' pattern. Despite the fact that BPDCN may initially appear as a localized skin tumour, aggressive management including allogeneic bone marrow transplantation should be considered immediately, as it is currently the only option associated with long-term survival.


Subject(s)
Dendritic Cells/pathology , Hematologic Neoplasms/pathology , Mouth Neoplasms/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Delayed Diagnosis , Female , Hematologic Neoplasms/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mouth Mucosa/pathology , Mouth Neoplasms/mortality , Retrospective Studies , Skin Neoplasms/mortality , Young Adult
3.
Br J Dermatol ; 162(1): 74-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19689477

ABSTRACT

Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) represents the malignant counterpart derived from plasmacytoid dendritic cells. This rare entity is usually revealed and diagnosed on cutaneous lesions associated or not with a leukaemic component. The prognosis associated with BPDCN is very poor. Objectives To perform a retrospective review of BPDCN cases registered in the French Study Group on Cutaneous Lymphoma database from June 1995 to May 2008. Methods Forty-seven patients were included. Demographic data, initial staging, therapeutic management and outcome were recorded. Results The mean survival was 16.7 months (95% confidence interval 12.6-20.8). Only eight (17%) and one (2%) patients reached respectively 2 and 5 years of survival. Initial spreading of the disease did not represent, in this cohort, a reliable prognosis factor. The outcome was overall influenced by treatment provided. While radiation therapy, monochemotherapy or even polychemotherapy regimens did not significantly affect the course of the disease, the survival of bone marrow transplanted patients was significantly higher. Conclusions Despite the fact that BPDCN is often initially limited to the skin, only an aggressive initial therapy may improve the patients' prognosis. Local treatments, such radiation therapy, are definitively useless. Regardless of the initial extension of the disease, in our experience only bone marrow transplantation significantly improved the outcome.


Subject(s)
Bone Marrow Transplantation , Dendritic Cells , Lymphoma/surgery , Skin Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Child , Cohort Studies , Female , Humans , Lymphoma/drug therapy , Lymphoma/mortality , Lymphoma/radiotherapy , Male , Middle Aged , Prognosis , Retrospective Studies , Skin Neoplasms/drug therapy , Skin Neoplasms/mortality , Skin Neoplasms/radiotherapy , Survival Analysis
4.
Leukemia ; 21(9): 2020-4, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17625611

ABSTRACT

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Genetic Heterogeneity , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Translocation, Genetic , Adult , Aged , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 4 , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Disease-Free Survival , Female , Follow-Up Studies , Hemoglobins , Humans , Male , Middle Aged , Multiple Myeloma/mortality , Multivariate Analysis , Prognosis , Retrospective Studies , Vincristine/administration & dosage , beta 2-Microglobulin/blood
5.
Ann Oncol ; 18(2): 370-5, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17074972

ABSTRACT

Single-agent gemcitabine has shown encouraging results in patients with mantle cell lymphoma (MCL). This phase II study further explored the potential of a gemcitabine-based regimen in patients with relapsed or refractory MCL. Patients <70 years old received the PDG regimen: gemcitabine (1000 mg/m(2), days 1 and 8), dexamethasone (40 mg/m(2), days 1-4), and cisplatin (100 mg/m(2), day 1). Patients >/=70 years of age received dexamethasone and gemcitabine only (DG regimen). Thirty patients (12 in the DG group, 18 in the PDG group) with a median age 66.5 years (range, 47-81) received a median of six cycles in both groups. The overall response rate was 36.4% [95% confidence interval (CI), 15.2% to 64.6%] with the DG regimen and 44.4% (95% CI 24.6% to 66.3%) with the PDG regimen. The median progression-free survival was 3 months (95% CI 0.0-7.9) in the DG group and 8.5 months (95% CI 4.8-12.2) in the PDG group. With a median follow-up of 38.8 months, 13 patients (including 11 given PDG) are still alive. DG was well tolerated, and thrombocytopenia was the most prevalent toxicity in patients receiving PDG. Both regimens deserve to be further investigated as a backbone for combination chemotherapy in patients with MCL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Dexamethasone/administration & dosage , Drug Resistance, Neoplasm , Female , Humans , Lymphoma, Mantle-Cell/metabolism , Male , Middle Aged , Remission Induction , Salvage Therapy , Treatment Outcome , Gemcitabine
6.
J Clin Pharm Ther ; 31(4): 389-92, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16882110

ABSTRACT

New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the first GO dose, a patient presented with ascites, weight gain, liver enlargement and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP and gamma-glutamyltransferase (GGT) respectively at four and eight times the normal range: grade 2] were observed but there was no evidence of increase serum bilirubin. Treatment with DF (Prociclide), Crinos; 10 mg/kg/day, or 200 mg, q.i.d.) improved the hepatic abnormality within a few days (serum transaminases decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141 to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from 253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of DF. The clinical and biological features of our case suggest a direct involvement of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell transplantation. Low dose DF (10 mg/kg/day) given early during the development of SOS associated with GO was effective. Unfortunately, in our case the patient eventually died of multi-organ failure probably because of failure of GO.


Subject(s)
Hepatic Veno-Occlusive Disease/chemically induced , Succinates/adverse effects , Aged , Fatal Outcome , Fibrinolytic Agents/therapeutic use , Hepatic Veno-Occlusive Disease/drug therapy , Hepatic Veno-Occlusive Disease/physiopathology , Humans , Leukemia, Myeloid/drug therapy , Male , Polydeoxyribonucleotides/therapeutic use
7.
Support Care Cancer ; 11(8): 539-47, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12783289

ABSTRACT

GOALS: To compare the efficacy and safety of ibandronate and pamidronate in patients with hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Seventy-two patients with HCM [albumin-corrected serum calcium (CSC) >2.7 mmol/l] were treated with a single infusion of ibandronate (2 or 4 mg) or pamidronate (15, 30, 60, or 90 mg) on day 0. The dose was dependent on the severity of hypercalcemia (baseline CSC level). CSC was assessed daily until day 4, then at intervals until day 28. The primary endpoint was lowering of CSC at day 4. Secondary endpoints included the number of patients responding and time to re-increase following response. MAIN RESULTS: Using the CSC baseline approach, the most frequently administered doses were 4 mg ibandronate (78.4%) and 60 mg pamidronate (50.0%). Mean lowering of CSC at day 4 was 0.6 mmol/l for ibandronate and 0.41 mmol/l for pamidronate. The 95% confidence interval for the difference ibandronate pamidronate had a lower limit of 0.05 mmol/l, indicating that ibandronate was as effective as pamidronate. The number of patients responding to the two agents was also similar; 76.5% of ibandronate patients and 75.8% of pamidronate patients were rated as responders after the first dose of study medication. The median time to re-increase after response was longer for ibandronate (14 days) than pamidronate (4 days) ( P=0.0303). In the subgroup of 17 patients with high baseline CSC (>3.5 mmol/l), ibandronate appeared to be more effective than pamidronate. The safety profile of both agents was similar. CONCLUSIONS: Ibandronate is at least as effective as pamidronate in the treatment of HCM. Furthermore, in patients with higher baseline CSC ibandronate appears to be more effective than pamidronate. The duration of response is significantly longer with ibandronate than pamidronate.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/pharmacology , Diphosphonates/adverse effects , Diphosphonates/pharmacology , Hypercalcemia/drug therapy , Hypercalcemia/etiology , Administration, Oral , Aged , Anti-Inflammatory Agents/administration & dosage , Bone Resorption , Diphosphonates/administration & dosage , Female , Humans , Ibandronic Acid , Male , Middle Aged , Neoplasms/complications , Pamidronate , Treatment Outcome
8.
Haematologica ; 84(12): 1075-80, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10586207

ABSTRACT

BACKGROUND AND OBJECTIVE: A small number of chronic myeloproliferative disorders with hematologic features of chronic myelomonocytic leukemia (CMML) or atypical chronic myeloid leukemia and Ph1 chromosome with m-BCR rearrangement have been reported (p190 CMPD). We report here 3 new cases of p190 CMPD that had unusual features. In 2 of the cases the m-BCR rearrangement appeared to be a secondary event. DESIGN AND METHODS: Patients were studied by cytogenetic, FISH, and molecular biology analyses and followed-up clinically. RESULTS: The first patient initially had typical 5q- syndrome, without m-BCR rearrangement. Five years later, she developed hematologic features of CMML, with t(9;22) translocation, m-BCR rearrangement and high levels of p190 BCR-ABL transcript. The second patient initially had hematologic characteristics of chronic myeloid leukemia (CML) with t(9;22) translocation and m-BCR rearrangement but also other complex cytogenetic findings including 17p rearrangement. Monocytosis developed during the course of the disease. The third patient initially had agnogenic myeloid metaplasia (AMM). Five years later, while the hematologic characteristics were still those of AMM, a first karyotype showed a t(9;22) translocation and molecular analysis showed a very low level of p190 BCR-ABL transcript. Four years later, the patient developed hematologic features of atypical CML with blood monocytosis, t(9;22) and much greater (100 fold) p190 BCR-ABL transcript levels. INTERPRETATION AND CONCLUSIONS: Our 3 cases and review of the previously published cases show the variability of clinical features of p190 positive CMPD. Our results also suggest that, at least in some cases, p190 BCR-ABL rearrangement could be a secondary event in the course of a myeloid disorder.


Subject(s)
Fusion Proteins, bcr-abl/genetics , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 9 , Cytogenetics , Female , Gene Rearrangement , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged , Philadelphia Chromosome , Translocation, Genetic
9.
Cancer Genet Cytogenet ; 111(2): 157-60, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10347555

ABSTRACT

We report four cases of follicular lymphoma with both t(14;18)(q32;q21) and the newly characterized t(3;4)(q27;p13). Molecular investigation confirmed LAZ3 (BCL6) rearrangement for all patients. The 3q27 aberrations have been rarely described in low-grade lymphomas and may represent secondary events whose implication remains to be elucidated.


Subject(s)
Chromosomes, Human , DNA-Binding Proteins/genetics , Lymphoma, Follicular/genetics , Proto-Oncogene Proteins/genetics , Transcription Factors/genetics , Translocation, Genetic , Adult , Aged , Blotting, Southern , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 18 , Chromosomes, Human, Pair 3 , Chromosomes, Human, Pair 4 , Female , Gene Rearrangement, B-Lymphocyte , Humans , Karyotyping , Lymphoma, Follicular/drug therapy , Lymphoma, Non-Hodgkin , Middle Aged , Proto-Oncogene Proteins c-bcl-6 , Zinc Fingers/genetics
10.
Br J Haematol ; 103(2): 512-7, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9827927

ABSTRACT

263 patients (median age 65+/-10 years) with multiple myeloma were treated with cyclophosphamide-prednisone. Out of this cohort, 103 patients had progressive disease and were randomly assigned to either VAD (vincristine, doxorubicin, dexamethasone; 50 cases) or VMBCP (vincristine, BCNU, cyclophosphamide, melphalan and prednisone; 53 cases). There were no statistical differences between the two groups with the respect to clinical, biological and radiological parameters. There was no difference in survival between the VAD and VMBCP groups. The 4 months response rate was similar in the two groups (50% VAD, 56% VMBCP). With multivariate analysis for survival (Cox model), two factors had a statistically significant impact: Karnofsky index (> 60) and albuminaemia (< 34 g/l). With both Karnofsky index > 60 and albuminaemia > or = 34 g/l, the median survival was 29 months v 2 months with a Karnofsky index < or = 60 and albuminaemia < 34 g/l (P<0.05). In conclusion, VAD or VMBCP had similar activity for salvage treatment in MM refractory or relapsing to first-line treatment with cyclophosphamide-prednisone.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Adult , Aged , Aged, 80 and over , Carmustine/administration & dosage , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Male , Melphalan/administration & dosage , Middle Aged , Prednisone/administration & dosage , Prognosis , Salvage Therapy , Survival Rate , Treatment Outcome , Vincristine/administration & dosage
13.
Rev Med Interne ; 14(10): 965, 1993.
Article in French | MEDLINE | ID: mdl-8009061

ABSTRACT

The diagnosis of idiopathic hypopituitarism in the elderly is difficult and often unrecognized. We report 6 cases.


Subject(s)
Hypopituitarism/diagnosis , Aged , Female , Humans , Male , Pituitary Gland, Anterior/physiopathology
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