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This report describes a case of congenital dyserythropoietic anemia (CDA) type I diagnosed in a 22-year-old woman with a two year history of macrocytic anemia. Light microscopy study of bone marrow disclosed only minor and nonspecific findings, without erythroid hyperplasia. Electron microscopy of bone marrow erythroblasts surprisingly showed most of the classical features of CDA type I. Electron microscopy may be an important tool for the diagnosis of macrocytic anemia of obscure origin, especially in young patients.

In contrast to intermediate- and high-grade non-Hodgkin's lymph-omas (NHL), patients with follicular lymphomas retain a poor prognosis in the long run. Several reports suggested that they are incurable by conventional chemotherapy. 10 patients with follicular NHL were autografted for consolidation of early remission. One of these patients treated in 1979 received the TACC regimen with unpurged marrow. The other 9 (8 in first, 1 in second remission) treated since July 1987 received the BEAM regimen followed by autologous bone marrow transplantation (ABMT) with marrow purged in vitro by mafosfamide at levels individually adjusted. There were no toxic deaths. 8 patients remain in unmaintained CR 15 to 43 months post-ABMT - 2 are beyond 2 years. The patient autografted in 1979 has relapsed 9 yr later. ABMT is feasible with no indue toxicity for consolidation of follicular NHL early in first remission, as an alternative aggressive strategy. Further studies and a longer follow-up will be needed to evaluate its antitumor efficacy.

Summary. We treated 47 adult patients with de novo myelodysplastic syndrome (MDS) by an anthracycline-AraC regimen. Median age was 54, and M/F 1·3. At diagnosis, 26 patients had refractory anaemia with an excess of blasts in transformation (RAEB-T) three had refractory anaemia (RA). 11 had refractory anaemia with excessive blasts (RAEB) and seven had chronic myelomonocytic leukaemia (CMML). Treatment was started within 3 months of diagnosis in 30 patients, and after more than 3 months in the 17 remaining patients. At the onset of treatment, 16 patients had progressed to acute myeloid leukaemia (AML). Twenty-two patients (47%) reached complete remission (CR), 10 (21%) had hypoplastic death and 15 (32%) had resistant disease. Median actuarial disease-free interval was 11 months. Median actuarial survival was 14 months from diagnosis and 10 months from the onset of treatment. A significantly higher CR rate was found in patients with RAEB-T at diagnosis (69%, v. 19%, in patients with other FAB subtypes: P= 0·008), and in patients treated within 3 months of diagnosis. Using multivariate analysis, RAEB-T at diagnosis emerged as the most powerful prognostic factor of CR achievement. Karyotype was the only significant prognostic factor of disease-free interval, with a median of 16·5 months in patients with normal karyotype versus 4 months in patients with abnormal findings (P= 0·018). A subgroup of 15 patients with RAEB-T at diagnosis and normal karyotype, who had a CR rate of 80% and a median actuarial disease-free interval of 18 months, could be identified. Our results confirm that, overall, intensive chemotherapy has limited efficacy in MDS, especially when compared with allogeneic bone marrow transplantation (BMT). Relatively favourable results were obtained in our patients with RAEB-T at diagnosis, however, particularly those with normal karyotype. In that subgroup, intensive chemotherapy may be recommended, especially before BMT, as a high risk of relapse after BMT in patients with RAEB-T allografted as first line therapy has been reported.

One of major hurdles to achieving good patient outcomes and survival rates in allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning is the high rate of transplant-related mortality (TRM). Much progress in supportive patient care has been accomplished over the last decade-notably the use of allelic HLA-matching (Yakoub-Agha, JCO 2006), the introduction of enteral nutrition (Seguy, Transplantation 2004), the development of wireless video-capsule endoscopy for the management of post-transplant diarrhea (Yakoub-Agha, Transplantation 2005), the availability of broad-spectrum antifungal prophylaxis, the use of busulfan IV instead of PO in the conditioning regimen, limitation of the use of ATG in graft-versus-host disease (GVHD) treatment and dose reduction when the latter drug is used in conditioning. Although all these various modifications have had a positive impact on short-term patient outcomes, their impact on long-term survival is still unclear. Hence, the main objective of the present study was to evaluate allo-CST outcomes as a function of the transplantation period. A total 445 patients have undergone post-myeloablation allo-CST in our department. The patient distribution over the time was as follows: prior to 1998 (first period): n=133; between 1998 and 2003 (second period): n=154; between 2003 and 2007 (third period): n=158. Only the first transplant for a given individual was taken into account. Kaplan-Meyer curves were plotted for 100-day survival, 180-day survival and 3-year survival for each time period. Setting aside the clear differences in supportive care methods, the three groups were well matched in terms of disease diagnosis, disease status at transplant and the main recipient and donor characteristics. It is noteworthy, however, that the median age of patients increased over time. Mean 100-day survival was 86 days (95% CI: 81–90), 93 days (95% CI: 90–96) and 96 days (95% CI: 94–98) for the first, second and third periods, respectively (p

Acute monocytic leukaemia (AMoL) was diagnosed in 99 adults, aged 18-85 years (median 56) over a period of 10 years. Sixty-five patients had extramedullary leukaemia, 13 had clinical signs of leucostasis, and 19 had disseminated intravascular coagulation. Four patients died before receiving any treatment, 12 received supportive care only and seven received low dose AraC, but only one of them responded. Seventy-six patients received intensive chemotherapy, 72 of them with an anthracycline-AraC based regimen, with or without an epipodophyllotoxin. Fifteen patients died within 7 d of diagnosis, due to leucostasis in nine cases. Predictive factors for early death were advanced age, leucostasis, fever, leucocytes above 100 x 10(9)/l, and renal failure. Fifty (66%) of the patients treated intensively reached complete remission (CR). Advanced age, fever and complex cytogenetic abnormalities were significantly associated with a lower CR rate. Median actuarial disease-free survival was 20.5 months, and was not significantly influenced by any pretreatment parameter. Five patients relapsed in the central nervous system (CNS), in spite of systematic CNS prophylaxis. No differences in CR rates were seen with the three anthracycline-AraC based regimens used in our patients. Significant differences in disease-free survival were seen between them, however, suggesting that early consolidation chemotherapy and, more hypothetically, epipodophyllotoxin agents could prolong remission duration in AMoL.

We treated 53 adults (mean age 54 years, range 17-89; 37 females and 16 males) with chronic idiopathic thrombocytopenic purpura (ITP) by azathioprine. All patients had received at least one form of therapy (including splenectomy in 40 patients) and had less than 50 x 10(9)/1 platelets. The duration of ITP before azathioprine was started ranged from 6 to 350 months (median 19). All patients initially received 150 mg/d of azathioprine. This was associated with a short initial course of prednisone (0.3-0.5 mg/kg d) in 10 of them, who were refractory to prednisone alone. 34 (64%) patients responded, including 24 (45%) complete remissions (CR), three (6%) partial remissions (PR) and seven (13%) minor responses (MR). Median time to achieve response was 4 months. 17 of the CR persisted after 7-182 months, 10 of them after discontinuation of azathioprine. Seven patients relapsed after 4-26 months, five of them after azathioprine was stopped or its dose was reduced. PR were short and the median duration of MR was 8 months. Overall, 21 patients (40%) had responses lasting 1 year or more and 17 (32%) lasting 2 years or more. Median duration of treatment was 18 months (range 3-84). Five patients died of bleeding while on treatment. No prognostic factors for response to azathioprine were found. Mild leucopenia was seen in seven patients and a moderate (x3) increase in transaminases in two patients. No opportunistic infections were seen and no malignancy has occurred since the onset of azathioprine. We conclude that azathioprine gives a relatively high incidence of durable responses and very limited side effects in chronic ITP, when splenectomy has failed or is contraindicated. This efficacy, in our experience, is superior to that obtained with other therapeutic approaches. As responses may be delayed, a course of azathioprine of 4 months is required before one can infer a failure to respond. In responding patients, however, the optimum duration of treatment remains to be established.

The results of the IFM 95-01 trial comparing MP to Dexamethasone-based regimens confirmed that the MP treatment remained the reference for patients (pts) older than 65 years with multiple myeloma (MM) (T. Facon et al., Blood 2005, in press). In May 2000, the IFM initiated a new trial, IFM 99-06, for pts aged 65–75 years, comparing MP (12 courses at 6 weeks intervals) to MP-THAL (MP plus THAL at the maximum tolerated dose, but d 400 mg/day, stopped at the end of MP) and a MEL100-based treatment (intermediate-dose MEL). The third arm’s schedule was VADx2, cyclophosphamide 3g/m2 for stem cell collection and 2 courses of MEL100 mg/m2. IFM99-06 was planned to enroll 476 pts for evaluation, whose treatment allocation followed a 3(MP)-2(MP-THAL)-2(MEL100) randomization scheme. The primary end-point was overall survival (OS), with two primary comparisons, MP vs MP-THAL and MP vs MEL100, and a secondary one, MP-THAL vs. MEL100. Secondary end-points were response to treatment and progression-free survival (PFS). Time-to-event curves were compared using the Cox model on an intent-to-treat basis and results expressed through hazard ratio (RR) with 95% confidence interval (95%CI). Two interim analyses were planned, according to Peto’s rule, after the enrollment of 200 and 350 pts, and reviewed by a Data Safety Monitoring Board (DSMB) independent of IFM. At the second interim analysis, the DSMB recommended the trial be pursued as planned, but suggested that a third interim analysis be performed with a date of point on May 1, 2005. At this time, 436 pts had been enrolled, 191, 124 and 121 in MP, MP-THAL and MEL100 groups, respectively. There were no differences in the distributions of pre-treatment characteristics between treatment groups, except for serum calcium level (P=0.02). The median (se) follow-up time was 32.2 (1.8) months (mo.), similar across groups. Median (se) PFS times were 17.1 (1.4), 27.6 (3.6) and 19.0 (1.2) mo. in MP, MP-THAL and MEL100 groups, respectively. The PFS time was significantly longer in the MP-THAL group than in the MP group (hazard ratio estimate, RR=2.4, 95% CI=1.8–3.3, P

Chronic myeloproliferative disorders (CMPD) are rare diseases of the bone marrow characterised by a clonal proliferation of one or several myeloid lineages. Familial clustering are regularly reported suggesting a role for inherited factors. To adress this issue, we collected with the help of a large network of haematologists clinical data and blood samples of 78 families defined by the presence of at least two affected subjects with one of the four CMPD: polycythemia vera, essential thombocythemia, chronic myeloid leukemia and agnogenic myeloid metaplasia. A total of 176 affected subjects including 83 polycythemia vera, 70 essential thrombocythemia, 12 chronic myeloid leukemia and 11 agnogenic myeloid metaplasia were recruited. 449 asymptomatic relatives, mainly first-degrees, were collected and among them 11%were carriers of endogenous erythroid colonies with normal blood counts. Phenotypic spectrum within families was either homogenous (46/78) or heterogeneous (32/78) and the main association (25/32) was polycythemia vera and essential thrombocythemia. A few cases of changes in disease phenotype was also observed during the course of CMPD. Clinical and haematological data of affected subjects at diagnosis and during the course of the disease were similar to sporadic CMPD. However, a marked anticipation of approximatively 20 years/generation at onset age was observed. No excess of carcinomas was noted either in affected subjects or relatives. An excess of acute leukemias, however, was noted in relatives. We did not show evidence of known environmental factors such as exposition to ionic radiations or chemical solvents. Familial cases were restricted to a single generation in 33 families. Occurence was vertical in 45 families involving 2 generations in 36 and 3 generations in 9. In those familial cases consistent with a dominant inheritance, we exluded molecular abnormalities of VHL and EpoR genes involved in particular forms of familial and congenital polycythemia. In conclusion, the analysis of these 78 familial CMPD cases highlights that (i) the observation of mixed phenotypes in a large proportion is consistent with the theory that MPD arise from clonal expansion of a pluripotent hematopoietic precursor cell (ii) no environmental factor is clearly involved in the onset of CMPD and (iii) the observation of familial aggregations and the low incidence of the pathology suggest the implication of genetic predisposition factors in the occurence of myeloproliferative disorders. This large collection of multiplex families enables us to initiate genome-wide linkage analysis.

Intoduction Due to the poor signal to noise ratio of MRI, there are no strong data pertaining to the validity of MRI techniques in the assessment of LIC in high post-transfusionnal iron overload. Moreover, reproducibility (from center to center) of this technique is not clearly established. We have compared chemically determined high LIC and two different MRI protocols of measuring LIC in patients transfused monthly: the first, to evaluate the exact reproducibility of a simple and widely recognized procedure used in hepatic diseases and the second, to improve sensitivity at higher LIC. Patients and Methods MRI method: MRI studies were performed using a 1.5 T system (Philips intera, The Netherlands). Transverse images were recorded, visualizing the right liver lobe (L) and posterior vertebral muscles (M) in the same slice. The signal intensity (SI) for hepatic tissue and the posterior vertebral muscle were determined. The L/M SI ratio (SIR) was then calculated. First procedure: Four magnetic resonance gradient echo sequences (T2++/t2+/PD/T1), exactly as previously published in hepatic disease studies (Gandon,Y Lancet 2004), were performed and the same software for LIC determination was used in order to evaluate the center to center reproducibility. Second procedure: EGT0.5 and EGT0 sequences using shorter echo times with the aim of improving accuracy at higher levels of iron overload were performed. Patients and liver biopsy: 21 liver biopsies were performed, after written consent, in 16 patients (MDS=4, b thalassemia=12). In the case of repeated biopsy, an interval of a minimum 12 months was respected between the two biopsies. Results: 21 biopsies, each more than one mg, in 16 adult patients (8 males, 8 females) with a median age of 41 (range 23–73 ). LIC ranged from 2.6 to 54mg/g liver dry weight (mg/gdw), (median 12.6 mg/gdw). Hepatic fibrosis and cirrhosis were histologically found in 4/21 and 4/21 cases, respectively. First procedure: In biopsies with LIC below 375 micromol/g dw (n= 14), a strong correlation was demonstrated between LIC and L/M SIR (r = 0.86), for the best sequence, similar to that previously reported (r =0.91). For the entire group, including cases with LIC > 375 micromole/g dw (n= 21), the correlation was not as good (r=0.72) as the previous group using the same sequence. Second procedure: EGT0.5: 4 cases having low LIC and SIR >1.5 were excluded. Among the 17 remaining cases, linear agreement between LIC and L/M SIR was excellent (r=0.89). EGT0: 16 cases had SIR Conclusion In mild post-transfusionnal iron overload, our results show: measurement by routine MRI produces an accurate and reproducible estimation of LIC from center to center, with the same level of correlation as previously reported, independent of the machine used. At high liver iron concentration (LIC> 375 micromol/gdw) (33% of our cases), some simple and rapid specific sequences can also provide an accurate measurement of LIC. These results suggest that, whatever the level of iron overload encountered, the LIC determination by simple and rapid routine MRI is more a question of the standardization than of the sensitivity of the method.

6636 Background: In this analysis, our main objectives were (1) to study the probability and the time needed to find a suitable unrelated donor or cord blood (2) to evaluate the impact of the time ...

Primary Sjogren’s syndrome (SS) is an autoimmune disease characterised by the presence of xerostomia and xerophthalmia without evidence of another systemic autoimmune disease. It has a wide clinical spectrum, extending from exocrinopathy to systemic autoimmune disease and to B cell lymphoma. The association of SS with aplastic anaemia (AA) has rarely been reported1 2 and only in patients with lymphoma. We report here an exceptional case of primary SS and severe AA without lymphoma who had cytogenetic and immunological abnormalities, which might give clues to the pathogenesis of ‘idiopathic’ AA. A 28 year old white man was referred in February 1990 for lymphadenopathies and pancytopenia. He complained of xerostomia and ocular burning. Xerophthalmia was confirmed by an abnormal Schirmer’s test (right eye 2 mm, left eye 1 mm after 10 mn) and a punctate keratitis on slit lamp examination after Rose-Bengal staining was observed. Labial salivary gland biopsy examination showed features of SS (grade 4 according to Chisholm’s focus score 3). A polyclonal hypergammaglobulinaemia with a low level of IgA was present and fluorescent antinuclear antibodies were positive in a titre of 1: 640 with a …

We report a case of congenital asplenia in an adult revealed by isolated thrombocytosis. The biological features might mimic a primary thrombocythemia.

A patient with sicle cells disease with bone marrow necrosis is reported. Favorable outcome is retail in spite of severe and multiple etiologies in this present case.

In order to estimate the incidence of Sjogren's syndrome, we prospectively performed labial salivary glands biopsy in 103 patients, HIV negative, with untreated non hodgkin's lymphoma. Clinical implications and immunopathological results will be discussed.

Seventy eight patients were systematically studied for thyroid function after bone marrow transplantation. We observed a slight increase of TSH in sixteen cases, on case of patent hypothyroidism, and four cases of hyperthyroidism. Characteristics of these thyroid dysfunctions are described.

Cerebrospinal fluid (CSF) neopterin concentrations were measured by HPLC in 44 normal children and 15 children affected by meningeal relapse of malignant hemopathy (13 acute lymphoblastic leukemia and 2 high grade lymphoma). When meningeal relapse was diagnosed, all the patients had CSF neopterin levels higher than the mean normal value + 2 SD, but no correlation was observed between CSF neopterin and blast count. In 10 children, CSF data before relapse were available : CSF neopterin at time of initial diagnosis of the hemopathy was 29.4 ± 12 nmol/l (median = 32.8) and 104.2 ± 56 (median = 85.6) when meningeal relapse (p < 0.01, Wilcoxon test). In 3 patients, elevation of CSF neopterin preceded (15 to 30 days) the occurrence of neurological signs or presence of blast cells in CSF. In absence of infectious context, a rise of CSF neopterin is an indicator of cerebral active phase of the malignant hemopathy. Such increase can reflect a cell mediated immunologic process induced by leukemic cells. The measure of CSF neopterin appears helpful in the monitoring of patients with malignant hemopathy to detect early meningeal relapse.

Between October 78 and November 90, we diagnosed angioimmunoblastic lymphadenopathy in 25 patients (11 females, 14 males, aged 26–89, median 60 years). Median survival was 26 months. Complete remission (CR) oblaining was found. Our study confirms the short survival of patients with AIL and the prognostic value of CR activement for survival.

In a prospective study 102 patients with untreated Multiple Myeloma (MM) stage I were evaluated for progression with a median follow-up of 48 months. Bone marrow plasmocytosis and hemoglobin level at the time of diagnosis could identify a subgroup of patients whose disease will remain stable for several years and a subgroup of patients with high risk of early progression.

Agnogenic myeloid metaplasia is often considered in patients with splenomegaly and severe myelofibrosis on bone marrow biopsy. However, other diagnoses must be suspected in patients without myelemia or splenic erythropoiesis, leading to splenectomy.

Lymphoblastic lymphomas are rare among adult patients. The onset of the disease may be acute and some patients rapidly need treatment. Age > 40 years, CNS involvement, B symptoms and initial high LDH level have a poor prognostic value.

Non-Hodgkin's lymphomas with testicular involvement are unfrequent. Most cases occur in elderly subjects and are of intermediate or high grade malignancy. Our study suggests that an early intensive chemotherapy improves survival. Lymphoblastic or Burkitt's lymphomas have a poor outcome and CNS relapses are frequent.

We report clinical, immunologic, and cytogenetic characteristics of six patients with a t(1;19)(q23;p13) that was balanced in one case and of the unbalanced type [−19,der (19)t(1;19)(q23;p13)] in the remaining five cases. Intracytoplasmic immunoglobulins (cIg) were positive in the three cases where they were found. We also report on another patient, with a t(17;19) involving 17q11 and probably 19q13 regions, although involvement of 19p13 could not be excluded. In this patient, cIg were also present, thus raising the issue of whether such a rearrangement could be a variant of t(1;19). Clinically, five patients belonged to the high-risk acute lymphoblastic leukemia (ALL) group, because of high leukocytosis, central nervous system (CNS) disease at presentation, or massive organomegaly. Cytologically, all cases were FAB type L1. Except for the two cases allografted in the first complete remission (CR) all patients relapsed, three of them within 13 months. Two CNS relapses were seen in spite of adequate CNS prophylaxis. ALL with t(1;19) appears to be a poor-risk ALL subgroup and probably requires a reinforcement of therapeutic modalities that might include, when possible, allografting at first CR.

In three cases of acute nonlymphocytic leukemia we observed a translocation (8;16)(p11;p13); in one case it was the sole karyotypic change and in the other two cases it was associated with other structural anomalies. All three cases were nonhyperleukocytic myelomonocytic leukemias with erythrophagocytosis by some blast cells and cytochemistry results consistent with leukemic proliferation of a common monocytic-granulocytic precursor. The importance of this translocation is discussed, and the implication of band 16p13 in myelomonocytic leukemia is stressed.

Resume Un inhibiteur de la coagulation de type anti-VIII: C est mis en evidence chez trois hommes non hemophiles de 75, 70 et 52 ans. Dans les trois case, le titre de l'anticorps est peu eleve (moins de 12,5 unites Bethesda au depart, moins de 20 unites au cours de l'evolution) et il persiste un taux faible mais detectable de VIII: C (7 a 12 p. 100 pour deux malades qui presentent des manifestations hemorragiques severes, 2 p. 100 pour le troisieme). Les 3 inhibiteurs inactivent le VIII: C selon une cinetique complexe de type II (Biggs and Coll). Les fractions antihemophiliques A a forte dose se revelent efficaces sur le plan biologique chez un malade mais ne parviennent pas a enrayer un saignement important. Les fractions plasmatiques activees sont utilisees avec succes a plusieurs reprises. Une fois, des doses moderees et repetees de fractions antihemophiliques A permettent une correction satisfaisante du taux de VIII: C et une intervention chirurgicale mineure. Un traitement immunosuppresseur est suivi 3 semaines chez un patient, 3 mois chez les deux autres. L'inhibiteur disparait dans les 3 cas apres 5 a 8 mois d'evolution. Le traitement des episodes hemorragiques chez les malades non hemophiles porteurs d'inhibiteur du VIII: C doit tenir compte de l'importance de l'accident d'abord et de la cinetique habituellement complexe de l'inhibiteur: il ne peut donc etre copie directement sur celui des inhibiteurs de type 1 de l'hemophile.

We report a promyelocytic blast crisis in a case of Ph-positive thrombocythemia with both t(9;22) and t(15;17). Our patient confirms the specificity of t(15;17) in malignant proliferation of promyelocytes and suggests its appearance as a second genetic event in the genesis of blast crisis occurring in a Ph-positive clone.

The authors report on five patients with secondary leukemia (SL) and one of the "specific" chromosomal rearrangements usually encountered in de novo acute nonlymphoblastic leukemia: inv(16), t(15;17), t(8;21), and t(9;11). They were characterized by solid tumor as the primary malignancy in four of five cases, absence of preleukemic phase in all cases, and myelodysplastic features in one of five cases only. All patients achieved complete remission (CR) with aggressive chemotherapy. Only two relapsed, but follow-up is still limited in the three remaining cases. Cytogenetic analysis is important in all younger patients with SL, especially if unusual features (such as absence of preleukemic phase or myelodysplastic features) are found. Aggressive chemotherapy appears to be indicated in those patients if a "specific" rearrangement is found.

We report two cases of translocation t(10;17)(p13;q12) found in a series of 278 cytogenetically studied acute nonlymphocytic leukemia cases. Blast cells, in both cases, were undifferentiated and had phagocytic properties. These patients might represent cases of a new cytogenetic entity.