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1.
Cancer Med ; 8(5): 2188-2195, 2019 05.
Article in English | MEDLINE | ID: mdl-30993891

ABSTRACT

We performed a retrospective analysis of 93 myelodysplastic syndromes (MDS) patients with intermediate 2 or high-risk IPSS score to study the impact of Azacitidine (AZA) relative dose intensity (RDI) <80% on the overall survival (OS). There were 51.6% of patients who had full dose and 48.4% had dose reduction or delayed with a RDI <80%. Nineteen patients (20.4%) had RDI <80% before getting objective response. Overall and progression-free survivals (OS, PFS) probabilities for the whole population were 58% (95% CI: 48-69) and 47% (95% CI: 38-58) at 1 year; 35% (95% CI: 26-47) and 31% (95% CI: 23-43) at two years, respectively. When analyzing the outcomes according to the response to AZA, median OS was 32 months (range: 26-55) for responders and 8 months (range: 7-12) for nonresponders, with a respective 1-year and 2-year OS probabilities of 91% vs 28% and 66% vs 6%, respectively (P < 0.001). Interestingly, there was no impact of dose reduction on OS nor on PFS, however, when analyzing the timing of dose reduction as time-dependent variable, we found that patients who had dose reduction before achieving the objective response, had significantly lower OS (P = 0.02) and PFS (P = 0.01) compared to patients who had dose reduction after achieving the objective response. In multivariate analysis, acute myeloid leukemia with 21%-30% blasts in BM and poor and very poor karyotype significantly impacted OS, (HR = 2.09, 95% CI: 1.27-3.44, P = 0.004, and HR = 2.73, 95% CI: 1.6-4.6, P < 0.001 respectively), as well as PFS (HR = 1.84, 95% CI: 1.07-3.17, P = 0.028, and HR = 3.03, 95% CI: 1.7-5.39, P < 0.001, respectively).


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Azacitidine/administration & dosage , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/mortality , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Azacitidine/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Survival Analysis , Treatment Outcome
2.
Ann Biol Clin (Paris) ; 76(4): 451-457, 2018 08 01.
Article in French | MEDLINE | ID: mdl-30078781

ABSTRACT

We report here a case of lymphoplasmacytic lymphoma with IgA paraproteinemia and a case of concomitant Waldenström macroglobulinemia and monoclonal gammapathy of unknown significance. These rare cases show that the isotype of a monoclonal immunoglobulin does not allow to foresee every time the underlying pathology. Clinical data and medical imaging are essential. From a biological point of view, additional analysis such as immunophenotyping, cytogenetics and molecular biology are required in addition to the cytological features in order to make an accurate differential diagnosis between lymphoid and plasma cell malignancy.


Subject(s)
Diagnostic Errors , Immunoglobulins/blood , Multiple Myeloma/diagnosis , Waldenstrom Macroglobulinemia/diagnosis , Diagnosis, Differential , Female , Humans , Immunoglobulins/analysis , Immunophenotyping , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/complications , Paraproteinemias/blood , Paraproteinemias/complications , Paraproteinemias/diagnosis , Waldenstrom Macroglobulinemia/blood , Waldenstrom Macroglobulinemia/complications
3.
Exp Hematol ; 65: 34-37, 2018 09.
Article in English | MEDLINE | ID: mdl-29883686

ABSTRACT

Iron overload has been associated with poor overall survival in patients with higher-risk myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation, but has not been investigated in higher-risk MDS patients treated with hypomethylating agents. We evaluated the prognostic value of serum ferritin levels at diagnosis in a retrospective analysis of 48 patients with an intermediate 2 or high-risk International Prognostic Scoring System (IPSS) score treated with azacytidine. overall survival probability at 1 and 2 years was 58% and 42%, respectively. When stratifying according to serum ferritin level at azacytidine initiation, patients with serum ferritin level <725 ng/mL had significantly better OS than those with serum ferritin level ≥725 ng/mL, with an overall survival probability of 74% (95% confidence interval [CI]: 58-94) versus 44% (95% CI: 28-68) at 1 year and 57% (95% CI: 39-81) versus 28% (95% CI: 15-52) at 2 years, respectively (p = 0.034). Median progression-free survival was 16.15 months (range: 9-26) for the entire cohort. Progression-free survival probabilities according to serum ferritin cut-off level <725 ng/mL or ≥725 ng/mL at 1 and 2 years were 70% (95% CI: 53-91) versus 44 (95% CI: 28-68) and 52% (95% CI: 35-77) versus 24% (95% CI: 12-48), respectively (p = 0.031). We have demonstrated that an serum ferritin level ≥725 ng/mL was associated with worse overall survival and progression-free survival when adjusting for other covariables in multivariate analysis, in addition, unfavorable karyotype led to worse outcome. In conclusion, we believe that that negative effect of serum ferritin level on overall survival is not only related to the iron toxicity, but most probably may also be considered as a surrogate marker for very ineffective erythropoiesis leading to marked anemia.


Subject(s)
Azacitidine/therapeutic use , Ferritins/blood , Myelodysplastic Syndromes/drug therapy , Risk Factors , Aged , Aged, 80 and over , Enzyme Inhibitors/therapeutic use , Female , Humans , Male , Prognosis , Treatment Outcome
4.
Ann Biol Clin (Paris) ; 76(4): 445-450, 2018 08 01.
Article in French | MEDLINE | ID: mdl-29905151

ABSTRACT

Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm defined by the presence of at least 5×109 G/L monoclonal B lymphocytes in the peripheral blood. It is the most common type of leukemia in adult patients from Western countries. CLL is characterized by a gradual accumulation of small, longliving, immunologically dysfunctional, morphologically mature-appearing B-lymphocytes in blood, bone marrow and lymphoid tissues. It has also been reported that CLL cells have a proliferation rate higher than previously recognized, particularly in the lymphoid tissues. The flow cytometry analysis of typical CLL identifies a monotypic B-cell population expressing a low level of surface immunoglobulins, light chain being either kappa or lambda-, CD5+, CD19+, CD23+, CD79b (dim), negative for FMC7 and CD10. Clinical presentation, course and outcome are highly variable. Interphase fluorescent in situ hybridization (I-FISH) identifies chromosomal abnormalities in about 80% of cases, most commonly involving 13q14 (55%), 11q22-23 (18%), or 17p13 deletions (7%) and trisomy 12 (16%). Therefore, five prognostic categories have been defined with a statistical model, showing the shortest median survival and treatment-free intervals in patients harboring 17p and 11q deletions, followed by trisomy 12 and a normal karyotype, whereas 13q deletion as the sole abnormality is associated with the best prognosis. We report here a rare case of CLL in a 54 year-old-man.


Subject(s)
Chromosomes, Human, Pair 12 , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Trisomy/diagnosis , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 18 , Cytogenetic Analysis , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Male , Middle Aged , Translocation, Genetic , Trisomy/genetics
6.
Hematol Oncol ; 35(4): 536-541, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27443419

ABSTRACT

Primary nodal marginal zone lymphoma (NMZL) is a rare disease. There is no current consensus on how to treat it. The bendamustine plus rituximab (BR) regimen is effective for the treatment of follicular and other indolent lymphomas, but its efficacy in NMZL is not known. We analyzed the outcome of 14 patients diagnosed with NMZL (median age 67 years) who were treated with 375 mg/m2 of rituximab on day 1 and 90 mg/m2 of bendamustine on days 1 and 2. The overall and complete response rates were 93% and 71%, respectively. Major toxicity (grade 3/4 neutropenia) occurred in 5% of treatment courses. After a median follow-up of 22 months (range: 18-55), the overall survival and the free survival rates were 100% and 93%, respectively. None of the patients showing a complete or partial response developed secondary myelodysplastic syndrome/acute myeloid leukemia. Bendamustine plus rituximab was found to be an active and well-tolerated regimen leading to the rapid control of disease.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Bendamustine Hydrochloride/therapeutic use , Lymphoma, B-Cell, Marginal Zone/drug therapy , Rituximab/therapeutic use , Aged , Aged, 80 and over , Female , Humans , Lymphoma, B-Cell, Marginal Zone/mortality , Male , Middle Aged , Survival Rate
7.
Ann Hematol ; 95(10): 1705-14, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27485454

ABSTRACT

Patients aged 80 or over with diffuse large B cell lymphoma (DLBCL) often have comorbidities that increase drug toxicity and prevent the use of otherwise optimal treatment. We performed a retrospective analysis of 43 patients aged 80 or over (median age: 83; range: 80-93) unable to receive treatment with anthracyclines, at diagnosis of DLBCL, treated with an R-CVP treatment (standard R-CHOP without doxorubicin). The patients had one or more comorbidities: 18 patients (41.9 %) had a performance status (PS) of 3; 23 patients (53.5 %) had low creatinine clearance; 12 patients (27.9 %) had low left ventricular ejection fraction; seven patients (16.3 %) had poor hepatic function; and 26 patients (60.5 %) had a Charlson index score ≥4. Thirty patients (70 %) had two or three adverse factors according to the age-adjusted International Prognostic Index. Twenty-five patients (58.1 %) received eight cycles of R-CVP, but the full eight cycles could not be given to 18 patients (41.9 %). The OR rate was 58.1 % (CR 37.2 %). There were 34 deaths (79 %) during treatment and follow-up. Ten patients (23.3 %) died early from toxicity before interim evaluation; all had PS 3. The median follow-up of surviving patients was 52.6 months. The overall 2-year survival rate was 31.9 % and the median OS was 12.6 months. The median OS for patients who completed the entire treatment was 26.4 months. The median PFS was 11.2 months. In multivariate analyses, OS was only affected by performance status ≥2 and Charlson index score ≥4. The R-CVP regimen can be active in elderly frail patients aged 80 or more with DLBCL, but systematic geriatric assessment is required so that those unsuitable for chemotherapy are excluded.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cardiovascular Diseases/chemically induced , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Frail Elderly , Hematologic Diseases/chemically induced , Humans , Infections/etiology , Kaplan-Meier Estimate , Kidney Diseases/chemically induced , Male , Prednisone/administration & dosage , Prednisone/adverse effects , Proportional Hazards Models , Retrospective Studies , Rituximab/administration & dosage , Rituximab/adverse effects , Salvage Therapy , Severity of Illness Index , Treatment Outcome , Vincristine/administration & dosage , Vincristine/adverse effects
8.
Biol Blood Marrow Transplant ; 22(8): 1357-1367, 2016 08.
Article in English | MEDLINE | ID: mdl-27026248

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. It is grouped with acute myeloid leukemia-related precursor neoplasms in the 2008 World Health Organization classification. Most patients with BPDCN have skin lesions at diagnosis and subsequent or simultaneous involvement of the bone marrow, peripheral blood, and lymph nodes. Patients usually respond to initial chemotherapy but often relapse. Stem cell transplantation may improve survival. This neoplasm is derived from precursors of plasmacytoid dendritic cells and is characterized by the coexpression of the immunophenotypic markers CD4, CD56, CD123, blood dendritic cell antigen-2, blood dendritic cell antigen-4, CD2AP, and lineage(-). Atypical immunophenotype expression may be present, making diagnosis difficult. BPDCN is often associated with a complex karyotype, frequent deletions of tumor suppressor genes, and mutations affecting either the DNA methylation or chromatin remodeling pathways. A better understanding of the etiology and pathophysiology of this neoplasm could open the way to new therapies targeting specific signaling pathways or involving epigenetics.


Subject(s)
Dendritic Cells/pathology , Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/pathology , Immunophenotyping , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Blast Crisis/pathology , Hematologic Neoplasms/classification , Hematologic Neoplasms/genetics , Humans , Leukemia, Myeloid, Acute/pathology , Skin Neoplasms , Stem Cell Transplantation
9.
Ann Hematol ; 95(5): 765-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26858026

ABSTRACT

We evaluated the efficacy and safety of rituximab for the treatment of 23 elderly patients (median age 78 years) with warm autoimmune haemolytic anaemia (AIHA). The median follow-up was 31 months. Patients had received one to five previous treatments. Rituximab was administered by intravenous infusion at a dose of 375 mg/m(2) once weekly for 4 weeks. The OR rate was 86.9 % (CR = 39.1 %, PR = 47.8 %). Median OS was 87 months. The median OS of patients who reached CR could not be calculated, and that of patients with PR was 67 months. At last follow-up, eight of the 20 responding patients, including one patient in CR and seven in PR, had relapsed after a median of 6 months. Failure to achieve CR was a risk factor for relapse (p = 0.028). We did not identify any pretreatment characteristics predictive of response to rituximab. In conclusion, rituximab is an effective treatment for elderly patients with refractory warm AIHA.


Subject(s)
Anemia, Hemolytic, Autoimmune/drug therapy , Immunosuppressive Agents/therapeutic use , Rituximab/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Aged , Aged, 80 and over , Anemia, Hemolytic, Autoimmune/immunology , Autoantibodies/immunology , Combined Modality Therapy , Disease-Free Survival , Drug Evaluation , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Kaplan-Meier Estimate , Male , Recurrence , Remission Induction , Retrospective Studies , Salvage Therapy , Splenectomy , Treatment Outcome
10.
Clin Case Rep ; 4(1): 39-42, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26783433

ABSTRACT

A patient with a marginal zone lymphoma received RCHOP and obtained PR. He received RDHAP, autograft, and obtained CR. Three months later, he developed Kaposi's sarcoma with spontaneous regression. Two months later, he developed DLBCL treated with R-MIV with CR. Thereafter, he developed AML and died a few days later.

11.
Clin Case Rep ; 3(2): 84-7, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25767702

ABSTRACT

A patient with multiple myeloma with a mass in the nasopharyngeal was diagnosed. He received melphalan autograft and radiotherapy, and obtained complete remission. He relapsed 3 months later, with meningeal involvement and without systemic relapse. He received intrathecal and systemic chemotherapy, without neurological improvement and died 4 weeks after relapse.

12.
Eur J Haematol ; 93(1): 81-5, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24571716

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy which was first included as an independent cutaneous lymphoma in the 2008 World Health Organisation (WHO) classification (1). BPDCN usually has an extremely poor prognosis, with quick relapses after chemotherapy (2; 3). Here, we report two cases of patients diagnosed in 2011 with BPDCN and myelodysplasia, and who were treated for the first time with 5-azacytidine (5-Aza); a drug approved by the Food and Drug Administration (FDA) and mainly used in the treatment of myelodysplastic syndrome (Kaminskas E, et al. 2005 Clin Cancer Res, 11, 3604-8). The first case was an 81-year-old man who presented with unusual CD10+, CD56- immunohistochemistry and 45X, -Y abnormality using fluorescent in situ hybridization (FISH) analysis. The second case was a 78-year-old woman who manifested monosomy 13 and chromosome instability due to D13S319 locus deletion in 13q14 as determined by FISH. Both patients showed excellent responses of their skin lesions after one cycle of chemotherapy, and their hematological disease was stabilized; however, pulmonary sepsis set in, followed by neutropenia after the fourth and the fifth cycle of treatment, that is, eight and 9 months postdiagnosis, respectively, leading to patient death.


Subject(s)
Azacitidine/therapeutic use , Hematologic Neoplasms/drug therapy , Aged , Aged, 80 and over , Female , Hematologic Neoplasms/pathology , Humans , Male
13.
Tunis Med ; 87(11): 737-41, 2009 Nov.
Article in French | MEDLINE | ID: mdl-20209830

ABSTRACT

BACKGROUND: Major Depressive Disorder (MDD) is often comorbid with personality disorders which are known to change its clinical aspects and worsen its outcome. AIM: This study aimed to compare clinical and outcome aspects of a female depressed inpatients group according to the existence or not of a comorbid personality disorder. METHODS: The study was carried in the psychiatry female inpatient unit of Farhat Hached hospital of Sousse. All entrances to the unit from January 1999 to August 2002 were retrospectively reviewed. 160, corresponding to MDD, were selected. Assessment was based on demographic characteristics, medical history, axis I comorbid disorders, clinical aspects of the index episode and outcome characteristics. RESULTS: 77 patients (48.1%) had personality disorder. Compared to those without comorbid personality disorder, these patients were younger (p < 10-4), with higher educational level (p = 0.005) and better vocational functioning (p = 0.018). They also had an earlier age at onset of their depression (p < 10-4), more previous suicide attempts (p = 0.012) and more axis I comorbid disorders (p < 10-4). Comorbid personality disorders were correlated to an impaired outcome, with higher rate of relapses (p = 0.021), more recurrences (p = 0.026), more persistent symptoms (p < 10-4) and more suicide attempts (p = 0.031).


Subject(s)
Depressive Disorder, Major/complications , Hospitalization , Personality Disorders/complications , Adult , Female , Hospital Units , Humans , Retrospective Studies , Tunisia
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