Inaugural tumor-like multiple sclerosis: clinical presentation and medium-term outcome in 87 patients.

BACKGROUND: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. METHODS: Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. RESULTS: Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). CONCLUSION: This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.

Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow.

Plasma therapy consists in bringing to a patient in need - in general suffering a severe, resistant to current therapy, and even lethal infection - plasma or specific, fractioned, antibodies, along with other immunoglobulins and possibly healing factors that can be obtained from immunized blood donors; donors (voluntary and benevolent) can be either actively immunized individuals or convalescent persons. Plasma therapy has been used since the Spanish flu in 1917-1918, and regularly then when viral epidemics threatened vulnerable populations, the last reported occurrence being the 2013-2015 Ebola virus outbreak in West Africa. The precise action mechanism of plasma therapy is not fully delineated as it may function beyond purified, neutralizing antibodies.

High numbers of mobilized CD34+ cells collected in AML in first remission are associated with high relapse risk irrespective of treatment with autologous peripheral blood SCT or autologous BMT.

The faster hematopoietic recovery after autologous peripheral blood SCT (APBSCT) in patients with AML may be offset by an increased relapse risk as compared with autologous BMT (ABMT). The EORTC and GIMEMA Leukemia Groups conducted a trial (AML-10) in which they compared, as second randomization, APBSCT and ABMT in first CR patients without an HLA compatible donor. A total of 292 patients were randomized. The 5-year DFS rate was 41% in the APBSCT arm and 46% in the ABMT arm with a hazard ratio (HR) of 1.17; 95% confidence interval=0.85-1.59; P=0.34. The 5-year cumulative relapse incidence was 56% vs 49% (P=0.26), and the 5-year OS 50% and 55% (P=0.6) in the APBSCT and ABMT groups, respectively. APBSCT was associated with significantly faster recovery of neutrophils and platelets, shorter duration of hospitalization, reduced need of transfusion packed RBC and less days of intravenous antibiotics. In both treatment groups, higher numbers of mobilized CD34+ cells were associated with a significantly higher relapse risk irrespective of the treatment given after the mobilization. Randomization between APBSCT and ABMT did not result in significantly different outcomes in terms of DFS, OS and relapse incidence.

[Cost per responder associated with romiplostim and rituximab treatment for adult primary immune thrombocytopenia in France]. / Coût par patient répondeur associé au traitement du purpura thrombopénique immunologique primaire par romiplostim et rituximab chez l'adulte en France.

PURPOSE OF THE STUDY: This analysis compared the response rates and cost per responder associated with romiplostim and rituximab in adult immune thrombocytopenia from the French National Health System payer perspective. METHODS: A decision analytic model was developed to estimate the cost per patient and per responder of treating adult immune thrombocytopenia patients with romiplostim versus rituximab over 6 months. A systematic literature review identified phase 3 randomized controlled trials. Published response rates were extracted (response definition: ≥50×10(9) platelets/liter). Resource utilization was based on French and international treatment guidelines, and clinical expert opinion. Unit costs were derived from literature and French reimbursement lists, and included the costs of routine physician visits, treatment administration, and emergency care. Non-responders incurred bleeding-related event costs. RESULTS: The literature review identified a phase 3 randomized controlled trial for romiplostim with a response rate of 83%. Due to a lack of phase 3 randomized controlled trials for rituximab, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. Romiplostim and rituximab were associated with similar treatment costs, with an estimated cost per patient for romiplostim of €17,456 and €17,068 for rituximab. Rituximab resulted in a 30% higher cost per responder (€27,308 for rituximab versus €21,031 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related hospitalization costs compared to rituximab. CONCLUSIONS: Due to its high efficacy leading to lower bleeding-related costs, romiplostim represents an efficient use of resources for adult immune thrombocytopenia patients in the French healthcare system.

Mycophenolate mofetil in multiple sclerosis: a multicentre retrospective study on 344 patients.

OBJECTIVES: Mycophenolate mofetil (MMF) is an immunosuppressive agent, sometimes used as a disease-modifying therapy for multiple sclerosis (MS). Several studies have reported the relative safety of this treatment but, to date, its efficacy has rarely been described. We performed a retrospective study to assess the safety and efficacy of MMF in patients with MS. METHODOLOGY: Three French MS centres included all of their patients treated by MMF. The main outcome criterion was annualised relapse rate (ARR) in the 1 year period after onset of MMF compared with the 1 year control period. Treatment with another immunosuppressive drug, such as mitoxantrone or cyclophosphamide, in the 2 years preceding initiation of MMF was included in a subgroup analysis. MMF safety and progression of the Expanded Disability Status Scale (EDSS) score were also assessed. RESULTS: 344 patients were included; 149 patients were previously treated with another immunosuppressant (IS group). Mean MMF treatment duration was 25.3±1.1 months. During the 1 year control period, ARR was 1.11±0.08, and for the 1 year treatment period, ARR was reduced significantly to 0.35±0.05 (p<0.0001, Wilcoxon paired test). Adverse events (occurring in 11% of patients) were mainly digestive disorders, benign infections, asthenia and transitory lymphopenia. Concerning the progression of disability, in the subgroup of patients without previous immunosuppressant treatment, EDSS remained stable between initiation and 1 year after the beginning of MMF. INTERPRETATION: Our results suggest that MMF can improve or stabilise MS patients and can be used as an alternative therapy.

A systematic review of available clinical evidence - filgrastim compared with lenograstim.

BACKGROUND: Filgrastim (Neu-pogen®, Amgen) and lenograstim (Granocyte®, Chugai Pharma) are chemically different granulocyte colony-stimulating factors (G-CSFs). Based on receptor-binding studies and in vitro potency assessment, a clinical superiority of lenograstim versus filgrastim has been postulated together with potential cost savings favouring lenograstim over filgrastim. OBJECTIVES: To compare the clinical efficacy of filgrastim and lenograstim based on current Summaries of Product Characteristics (SPCs) for both products taking into account published clinical trials in patients and healthy volunteers. SEARCH STRATEGY AND SELECTION CRITERIA: PubMed and citation lists of published articles were used to identify clinical trials with direct comparisons of filgrastim and lenograstim. All available clinical information directly comparing filgrastim and lenograstim has been accepted for evaluation. DATA COLLECTION: A total of 16 studies compared filgrastim with lenograstim. Four studies had a randomized, parallel-group design, 4 had a cross-over design and 8 studies were uncontrolled. RESULTS: Available data do not suggest a clinically remarkable difference between filgrastim and lenograstim in chemotherapy-induced neutropenia and the mobilisation of peripheral blood progenitor cells (PBPC) in patients and healthy donors. CONCLUSIONS: Both G-CSFs are recommended for clinical use according to instructions in the respective SPCs; there is no reason to prefer lenograstim over filgrastim in any of the approved indications for both. Costs calculations need to consider the advent of biosimilar filgrastim in Europe.

Intensive and prolonged treatment of focal and segmental glomerulosclerosis recurrence in adult kidney transplant recipients: a pilot study.

No treatment has consistently induced long-term remission of proteinuria in adult patients with focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation. We undertook an open-label, nonrandomized pilot trial of intensive and prolonged treatment of FSGS recurrence. Over an 18-month period, 10 adult kidney transplant recipients with FSGS recurrence received concomitantly high-dose steroids, intravenous cyclosporine for 14 days followed by oral cyclosporine therapy, and an intensive and prolonged course of plasma exchanges (PE). We compared this treatment with those of a control group of 19 patients with a FSGS recurrence transplanted between 1997 and 2005. Complete, rapid (mean 23 +/- 7 days) and sustained remission was obtained in 9/10 patients (90%) as opposed to 27% in the control group. At month 3 and month 12, proteinuria was 0.16 g/day (range 0.05-0.3 g/day) and 0.19 g/day (range 0.05-1 g/day) respectively. Only one patient remained in partial remission at month 12 but he had already lost two previous grafts due to FSGS recurrence. PEs were stopped at month 9 in all patients except for the patient with a partial remission who remains PE-dependent. This small pilot study provides very encouraging results demonstrating that this treatment rapidly achieves complete and sustained remission in a high proportion of patients.

Pulmonary hypertension associated with myeloproliferative disorders: a retrospective study of ten cases.

BACKGROUND: Pulmonary hypertension (PH) is a severe hemodynamic disorder in which the pulmonary artery pressure is persistently elevated, leading to right-sided heart failure. Some studies have suggested an association between PH and myeloproliferative diseases (MPD). OBJECTIVES: This study describes clinical, hematological and hemodynamic characteristics of PH associated with MPD. METHODS: We retrospectively reviewed 10 cases of PH associated with MPD: polycythemia vera (8 patients) and essential thrombocythemia (2 patients), followed between 1993 and 2002. The baseline evaluation was established by right-sided heart catheterization, ventilation/perfusion lung scan and pulmonary angiography if required. RESULTS: Six patients had confirmed chronic thromboembolic pulmonary hypertension (CTEPH) and 4 had pulmonary arterial hypertension (PAH) associated with MPD without other risk factors for PAH. The hemodynamic characteristics of CTEPH and PAH associated with MPD were similar. The diagnosis of CTEPH was concomitant to that of MPD in all cases (5 polycythemia vera and 1 essential thrombocythemia). The PAH associated with MPD occurred later in the evolution of the MPD (3 polycythemia vera and 1 essential thrombocythemia) with a median of 162 months after the diagnosis of MPD, and it was associated with myeloid metaplasia (p < 0.01). CONCLUSION: We describe 2 distinct forms of PH in the context of MPD: CTEPH, which is diagnosed at an early stage of the MPD, and PAH, which occurs later in the course of the MPD and is associated with myeloid metaplasia. Progressively increasing dyspnea in a patient with an MPD warrants further investigation to rule out PAH and CTEPH, while a diagnosis of CTEPH warrants ruling out MPD.

[Increased risk of relapse in multiple sclerosis patients after ovarian stimulation for in vitro fertilization]. / Augmentation du risque de poussée de sclérose en plaques après stimulation ovarienne pour fécondation in vitro.

In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial.

In this trial, acute myeloid leukemia patients (pts) aged 61-80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P=0.15, hazard ratio (HR) =1.18, 95% confidence interval (CI) 0.94-1.49) - primary end point - and survival (median 15.7 vs 17.8 months, P=0.19, HR=1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting (10 vs 2%; P=0.001) and diarrhea (10 vs 4%; P=0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery >20 x 10(9)/l (median: 19 vs 23 days; P=0.02) and duration of hospitalization (mean: 15 vs 27 days; P<0.0001) was shorter. The 'non-infusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.

The VAD chemotherapy regimen plus a G-CSF dose of 10 microg/kg is as effective and less toxic than high-dose cyclophosphamide plus a G-CSF dose of 5 microg/kg for progenitor cell mobilization: results from a monocentric study of 82 patients.

A study was conducted to compare the efficiency and toxicity of two peripheral blood stem cell (PBSC) mobilization procedures for newly diagnosed patients with multiple myeloma. Patients from group 1 (n=51) were treated by high-dose cyclophosphamide (HD-CY) plus G-CSF (5 microg/kg/day), and the second group (n=31) by VAD regimen plus G-CSF administration (10 microg/kg/day). Successful mobilization, defined by a minimal count of 2.5 x 10(6) CD34(+) cells/kg collected, was achieved in 96 and 90% of patients in groups 1 and 2, respectively (P=0.15). The mean peripheral blood CD34(+) cells concentration and the mean CD34(+) cells/kg collected were higher in group 2 than in the group 1 (P=0.05). The mean number of leukaphereses necessary to collect a count of 2.5 x 10(6) CD34(+) cells/kg was reduced in group 2 compared to group 1. Adverse events, blood products consumption and time spent in the hospital were significantly greater after HD-CY. In conclusion, VAD plus a G-CSF dose of 10 microg/kg administration seems preferential to HD-CY plus a G-CSF dose of 5 microg/kg for PBSC collection because of equivalent or better efficiency in stem cell mobilization, strong favorable toxicity profile and reduced cost.

Primary follicular lymphoma of the gastrointestinal tract: a study of 25 cases and a literature review.

BACKGROUND: To describe better the clinical, biological, endoscopic and pathological presentations, as well as the outcome, of primary follicular lymphoma (FL) of the gastrointestinal (GI) tract. PATIENTS AND METHODS: From November 1983 to February 2001, 25 eligible patients with primary FL of the GI tract were retrieved from several French Departments of Pathology departments based on histological diagnosis and immunophenotype. Median age was 56 years (range 44-71) with a sex ratio female/male of 2 (17/8). RESULTS: Abdominal pain was the main presenting symptom followed by intestinal obstruction. The small intestine was the most common site of involvement. Lesions were unifocal in the majority of patients (15/25). A pattern similar to lymphomatous polyposis was observed in 50% (7/14) of patients. Twelve patients had stage I, 10 patients stage II and three patients stage IV disease, and there was minimal extra intestinal involvement. Lymphoma tissues were composed of neoplastic follicles, most of which were grade 1 according to the World Health Organization (WHO) classification. The immunophenotype of the lymphoma cells was CD20+, CD10+, bcl2+ and CD5-. In tissue samples, IgH/bcl2 rearrangement at the MBR locus was present in 11 of 14 patients tested. Seven patients did not receive any treatment; four of them progressed after a median follow-up of 37.5 months. Treatment was otherwise heterogeneous, and complete remission was obtained in 15 patients which lasted for a median of 31 months. Relapses were either in the GI tract (n = 3) or outside the GI tract (n = 3). After a median follow-up of 34 months (range 5-203), 22 patients were still alive (complete remission, 11; partial remission, three; stable disease, six; progressive disease, two). CONCLUSIONS: Primary FL of the GI tract is a predominantly female lymphoma that most frequently involves the small intestine. Since the endoscopic and clinical presentation may not be different from lymphomatous polyposis, which is often associated with mantle cell origin of tumor cells, it is mandatory to perform an immunohistological and, if possible, a molecular analysis of GI lymphoma. The course of the disease is indolent and does not differ from nodal FL. Thus, therapy may not be required unless significant clinical symptoms are present or until disease progression.

Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts: results from APL 93 trial.

Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by comparison with CT alone. ATRA syndrome is a life-threatening complication of ATRA treatment whose prophylaxis remains somewhat controversial. In APL93 trial, newly diagnosed APL patients CT) and ATRA with early addition of CT, on day 3 of ATRA treatment (ATRA + CT). The incidence of ATRA syndrome in the ATRA --> CT arm was 18% (22/122) as compared to 9.2% (17/184) in the ATRA + CT arm (P = 0.035). In the ATRA --> CT arm, three (2.5%) patients died from ATRA syndrome, as compared to one (0.5%) in the ATRA + CT group. Early addition of chemotherapy to ATRA in newly diagnosed APL with low WBC counts significantly reduced the incidence of ATRA syndrome.

Remission of transformed myelodysplastic syndrome with fibrosis after danazol therapy.

Danazol has been used with success in some hematological diseases, but there is no report of this treatment in acute leukemia. We report here a case of remission of myelodysplastic syndrome with myelofibrosis in transformation after danazol therapy in a 72-yr-old man. The role of danazol in remission induction is briefly discussed.

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study.

Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twenty-five patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.

[Formal thought disorders: French translation of the Thought, Language and Communication assessment scale]. / Troubles formels de la pensée: traduction française de l'échelle d'évaluation de la pensée, du langage et de la communication.

This article proposes a french translation of Andreasen's Thought, Language and Communication (TLC) scale (Andreasen, 1979). This scale is widely used in current literature and remains a reference due to the fact that it has made it possible to establish a consensus with regard to formal thought disorders and has contributed to the operationalisation of the concept of dissociation. This scale consists of 18 items. Each item is clearly defined through the use of clinical examples, rated from 0 to 4 as a function of the intensity of the disorder (absent, slight, medium, severe, extreme). The interview conditions are also stated: free interview of minimum 10 minutes followed by a more structured interview. Some items of the TLC are taken directly from the SANS and SAPS. Their translation has been taken over from french translations already validated by Lecrubier and Boyer (1987). The others were translated within the department and have been verified by a native English speaker. The entirely of the translation has been verified by Andreasen. The metrological qualities of this french translation have been studied in a population of 107 schizophrenic patients who fulfilled all the DSM IV criteria: 73 males and 34 females, mean age 33.4 9 years, in or outpatients, all under neuroleptic treatment and all evaluated by an experienced clinician. Thirty one patients have been filmed to assess the interjudge reliability. The results indicate a high level of interjudge consistency (interclass correlation coefficient 0.96). The global score was 17 9.4. In the factorial analysis before rotation we observe a main factor that makes it possible to calculate a global score. The results of factor analysis of the TLC variables after rotation yield five factors that have an eigen value greater than 1. These five factors explain 66% of the variance. All items have a weight greater than 0.45. The first factor includes Poverty of content speech, Tangentiality, Derailment, Incoherence, Illogical thinking, Loss of goal and Perseveration. It reflects thinking disorganisation. The second factor includes Pressure of speech, Circumstantiality, Self reference and Poverty of speech (negative weight). This factor reflects verbal production. The third factor is composed of Clanging, Neologisms, Word approximation and Echolalia. This factor reflects verbal structure. The fourth factor is only composed of Stilted speech and the fifth one composed of Distractible speech and Blocking. These data have been compared to those reported in the literature: Andreasen in 1979 (113 patients: 32 suffering from manic disorder, 36 from depressive disorder and 45 schizophrenic disorder) and in 1986 (194 subjects: 94 controls, 25 suffering from manic disorder, 25 schizoaffective disorder and 50 schizophrenic patients), Harvey in 1992 (115 schizophrenic patients) and Peralta in 1992 (142 schizophrenic patients). Response levels for each item of the TLC french translation were very close to those found in the english versions. Differences in scores can be explained by clinical differences between populations studied. Factorial analyses also correspond well to such versions. In particular, after rotation, the three factorial subscores found representative of disorganisation, verbal production and verbal structure respectively are closed to those proposed by the english versions. In conclusion, the translation of Andreasen's Thought, Language and Communication (TLC) scale (Andreasen 1979) that we propose here therefore appears to exhibit metrological qualities sufficiently close to those reported in literature to permit its generalised use in France.

Typical essential thrombocythaemia does not express bcr-abelson fusion transcript.

Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder (MPD) characterized by an elevated platelet count and no identifiable underlying primary cause. According to the diagnostic criteria of the Polycythemia Vera Study Group (PVSG), ET lacks features diagnostic for other MPDs, including the Philadelphia chromosome (Ph) or bcr-abl rearrangement. Recently, some authors have reported bcr-abl transcript positivity in ET patients, but these findings remain controversial. The aim of this study was to investigate whether the bcr-abl transcript could be found in ET patients and to verify the hypothesis of a new ET variant. ET patients (n = 121) with a median age at diagnosis of 55 years were enrolled. The bcr-abl transcript status was examined by multiplex reverse transcription-polymerase chain reaction. Only two cases were positive for bcr-abl, one of which had the Ph at diagnosis. The positive bcr-abl transcript was associated, in both cases, with mild basophilia at diagnosis. After a median follow-up of 43 months (0-309 months), two patients in the bcr-abl-negative group developed Ph and bcr-abl-negative acute myeloid leukaemia (AML). In contrast, one of the two patients in the bcr-abl-positive group died from AML 13 years after diagnosis. In conclusion, our data on a large group of patients shows the rarity of the bcr-abl transcript in well-established ET. However, a subset of patients with apparent ET and basophilia may express the transcript and may constitute a novel entity intermediate between chronic myeloid leukaemia (CML) and typical ET. A prospective study is warranted in order to define better the clinical and biological characteristics of bcr-abl-expressing ET.

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype.

The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P <0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI > or =2 had 8 months median OS as compared to 36 months median OS for patients with IPI <2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5+ NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients.