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Intravascular large B cell lymphoma is a neoplastic cell proliferation leading to the occlusion of the lumen of small vessels. This is a rare haematological malignancy, which is difficult to diagnose because of a heterogeneous clinical presentation.We report a 62-year-old man who presented a macrophage activation syndrome as the presenting manifestation of an intravascular lymphoma. This association is frequently marked by a greater severity and clinical care requires an early and appropriate treatment.Due to the polymorphism and the systemic presentation of intravascular large B cell lymphoma, the internist may be confronted with this disease, which is considered to be more severe if associated with a macrophage activation syndrome. Awareness of the intravascular large B cell lymphoma is important because the prognosis depends on the rapidity of the initiation of chemotherapy associated with rituximab.

Overall survival of patients with Hodgkin lymphoma has dramatically increased in recent years, with an increased rate of malignant complications. We report here a 54-year-old man who presented with concomitant relapse of classical Hodgkin's lymphoma and lung adenocarcinoma 20 years after initial treatment with chemotherapy and mantle radiotherapy. Pathogenic mechanisms of these malignant complications are discussed. A prolonged follow-up of patients with Hodgkin's lymphoma is required.

In patients with hematological malignancy (HM) developing acute respiratory failure (ARF) bronchoalveolar lavage (BAL) is considered as a major diagnostic tool. However, the benefit/risk ratio of this invasive procedure is probably lower in the subset of patients with acute myeloid leukemia (AML). The study was to analyze the yield of BAL performed in HM patients (n=175) with AML or lymphoid malignancies (LM) admitted in intensive care unit (ICU) for ARF and pulmonary infiltrates. BAL was performed in 121 patients (53/73 AML patients (73%) and 68/102 LM patients (67%)) without a definite diagnosis at admission or contraindication for fiberoptic bronchoscopy. Life-threatening complications were noticed in 12/121 patients (10%). The overall diagnostic yield of BAL was 47% (25/53) in AML patients and 50% (34/68) in LM patients. A microorganism was recovered from BAL in 23% (12/53) of AML patients and 41% (28/68) of LM patients (P

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m(-2) day(-1) was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m(-2) day(-1). Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m(-2) day(-1) for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m(-2), and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m(-2) day(-1). The mean half-life of ssHHT was 11.01+/-3.4 h, the volume of distribution at steady state was 2+/-1.4 l kg(-1) and the plasma clearance was 11.6+/-10.4 l h(-1). Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m(-2) day(-1).

Summary Background Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT). Method We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients. Findings 199 centres gave information relating to 19 412 allogeneic and 17 950 autologous transplant patients. 232 (0·6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1·7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference=26% [95% CI 15–38]), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% [4–24]), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% [6–29]). Interpretation Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.

The epidemiology and clinical outcome of acute myeloid leukaemia in human immunodeficiency virus (HIV)-infected adults is poorly documented. We retrospectively surveyed all French haematology centres for adult acute myeloid leukaemia (AML) cases diagnosed between January 1990 and July 1996 who were found to be HIV-seropositive before or at the time of AML diagnosis. Medical charts were reviewed to determine the stage of HIV infection, the characteristics of AML and the response of AML to chemotherapy. Sixteen cases of AML (13 men, three women) were reported by 12 haematology units. Based on assumptions on the size, age and sex distribution of the HIV-infected population in France, the estimated risk of AML in 1990 to 1996 among HIV-infected adults was twice that of the general population (standardized incidence ratio = 2.05; 95% confidence interval, 1.17-3.34). Two other cases occurring before 1990 were spontaneously notified to the authors and were included in the clinical analysis. At AML diagnosis, the median CD4+ cell count was 275 x 106/l and nine patients had acquired immune deficiency syndrome (AIDS). Fifteen patients were scheduled for remission-induction therapy of AML. No deaths were related to AML treatment. Complete remission was obtained in 11 out of 15 patients. Three patients were long-term survivors: two remain alive in complete remission at 8 years and 9 years, respectively, and the third died of AIDS at 8 years. A CD4+ cell count above 200 x 106/l at AML diagnosis was predictive of longer survival (log-rank test: P = 0.004). Like many other malignancies, the incidence of AML appears to be increased in HIV-infected patients. Our results show a twofold higher incidence, although this needs to be confirmed in a specifically designed prospective epidemiological study. Such patients, especially those with CD4+ cell counts above 200 x 106/l at AML diagnosis, should receive remission-induction therapy, which can confer long-term survival.

A total of 193 patients with acute myelocytic leukaemia (AML) [147 in first complete remission (CR1)], ranging from 60 years to 75 years of age (median 63 years), were autografted between January 1984 and December 1998. The source of stem cells was peripheral blood (PB) in 128 patients, bone marrow in 51 patients and a combination of both in 14 patients. Total body irradiation (TBI) was used in 34 cases. Ninety-seven per cent of patients had successful engraftment of neutrophils on day 15 (range days 7-71) and of platelets on day 30 (range days 9-894). In patients autografted in CR1, the transplant-related mortality (TRM) was 15 +/- 4%, the relapse incidence (RI) was 58 +/- 5%, the leukaemia-free survival (LFS) was 36 +/- 5% and the overall survival was 47 +/- 5% at 3 years. The source and dose of stem cells were studied in particular; in patients transplanted in CR1, the RI was 44 +/- 11% in those receiving marrow compared with 63 +/- 6% in those receiving PB (P = 0.04). Patients autografted in CR1 who received higher granulocyte-macrophage colony-forming units (CFU-GM) doses (above the median) had a lower RI (47 +/- 11% vs. 79 +/- 9%, P = 0.009). There was a significant improvement in patients transplanted after March 1996; for those in CR1, the RI was 41 +/- 8% vs. 65 +/- 6% (P = 0.01), the LFS was 53 +/- 8% vs. 28 +/- 5% (P = 0.01) and the overall survival was 72 +/- 7% vs. 36 +/- 6% (P = 0.02). By multivariate analyses, significant factors for the outcome were the date of transplant with recent improvement and the source of stem cells, with a lower RI for marrow. Autologous stem cell transplantation (ASCT) is a potential therapeutic approach in patients with AML over 60 years of age; results have improved recently.

Aim In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT. Patients and Methods Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n=182) and acute lymphoblastic leukemia (ALL, n=144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 ± 11, range: 3 to 63). The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group (≤0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and ≤ 0.09 Gy/min), and 20 in the HIGH group (> 0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 ± 29, range: 24 to 130 months). Results Five-year survival, LFS, RI and TRM rates were 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW group, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five-year RI was 50% in STBI, 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03: MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%: p = 0.002 and 0.02, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age ≤ 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GvHD was the only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008). Conclusion The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy mainly rely upon prognostic factors, and their importance is constantly reassessed. To examine the impact of time from diagnosis to transplant on survival and leukemia-free survival (LFS), we analyzed 109 patients from the database of the SFGM comprising patients who had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first complete remission (CR1) between January 1987 and December 1992. All patients were conditioned with cyclophosphamide (CY) and total body irradiation (TBI) (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus-host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9, M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6. Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had other abnormalities. Eleven patients needed two courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients developed gradeor = 2 acute GVHD (actuarial probability = 46%). With a median follow-up of 50 months (27-100), the 5-year probabilities for transplant-related mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59% and 55%. A multivariate analysis showed that survival is adversely influenced by three independent factors: time to transplant (120 days vsor = 120 days), acute GVHD (grade 2-4 vs grade 0-1) and age (33 vsor = 33). LFS is only influenced by the first two of these factors. The favorable impact of a shorter time from diagnosis to transplant should lead to performing the transplant as early as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should begin immediately and transplant be performed as soon as possible.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of haematopoietic stem cells. Although knowledge about the pathophysiology of the disease is increasing, no multivariate analysis of factors influencing survival has been undertaken, mainly because the disease is rare. We undertook such an investigation.Data were collected on 220 patients with PNH diagnosed over a 46-year period (1950-1995) from participating French centres. Diagnosis of the disease required, at least, an unequivocally positive Ham's test.The Kaplan-Meier survival estimate was 65% (SE 4) at 10 years and 48% (6) at 15 years after diagnosis. 8-year cumulative incidence rates of the main complications (pancytopenia, thrombosis, and myelodysplastic syndrome) were 15% (3), 28% (4), and 5% (2), respectively. Demographic data, presenting features, initial treatment, complications, and causes of death were similar to those previously reported. In multivariate analysis, seven factors were significantly associated with survival in patients with PNH. Poor survival was associated with the occurrence of thrombosis as a complication (relative risk 10.2 [95% CI 6-17], p0.0001), evolution to pancytopenia (5.5 [2.8-11], p0.0001), myelodysplastic syndrome or acute leukaemia (19.1 [7.3-50], p0.001), age over 55 years at diagnosis (4 [2.4-6.9], p0.0001), need for additional treatment (2.1 [1.3-3.6], p0.003), and thrombocytopenia at diagnosis (2.2 [1.3-3.8, p0.003). Better survival was shown for patients in whom aplastic anaemia antedated PNH (0.32 [0.14-0.72], p0.02). Factors associated in multivariate analysis with a high risk of thrombosis during the disease course were thrombosis at diagnosis (5.1 [2.5-10.6], p = 0.0002), age over 54 years (2.6 [1.5-4.6, p = 0.0014), and infection at diagnosis (2.6 [1.3-5.2], p = 0.0099). The risk factors for progression to pancytopenia were absence at diagnosis of anaemia (4.03 [1.3-12.2], p = 0.03) and neutropenia (2.45 [1.1-5.7], p = 0.03). The risk factors for development of myelodysplastic syndrome or acute leukaemia were abdominal pain crisis at presentation (10.5 [2.5-44.0], p = 0.004) and year of diagnosis after 1983 (8.45 [1.8-40.7], p = 0.004).This large number of cases permitted a detailed analysis of prognostic factors for the first time, in this rare disease. Estimates of PNH prognostic factors may serve as baseline data in the assessment of current and future treatments for this disease.

In order to assess the influence of total-body irradiation technique on veno-occlusive disease (VOD) incidence, we retrospectively analyzed our leukemia patients treated with bone-marrow transplantation conditioned using total-body irradiation and high-dose chemotherapy.Between 1980 and 1992, 305 patients with acute non-lymphoblastic leukemia (ANLL; n = 170) and acute lymphoblastic leukemia (ALL; n = 135) were treated with bone-marrow transplantation in their first complete remission (CR; n = 223) or in second CR (n = 82). All patients underwent total-body irradiation either in single dose (n = 176; 10 Gy to L4, 8 Gy to the lungs) or in 6 fractions (n = 129; 12 Gy in 3 consecutive days to L4, 9 Gy to the lungs) before bone-marrow transplantation. Patients were analyzed in 2 instantaneous dose rate groups: 104 (34%) patients received an instantaneous dose rateor = 4.80 cGy/min (mean: 3.07 +/- 0.60 cGy/min), and 201 (66%)4.80 cGy/min (mean: 6.60 cGy/min +/- 0.30). Conditioning chemotherapy consisted of cyclophosphamide alone in 231 patients, cyclophosphamide and etoposide or melphalan in 53 patients, and 21 patients were conditioned with cytosine arabinoside and melphalan. Bone-marrow transplantation was autologous in 197 patients, and allogeneic in 108 patients.Thirty (10%) of the 305 patients experienced VOD. In univariate analyses, its incidence was not influenced by instantaneous dose rate (9.6% [10/104] inor = 4.80 cGy/min group vs. 10% [20/201] in4.80 cGy/min group; p = 0.91), fractionation (11% [19/176] in single-dose total-body irradiation vs. 8.5% [11/129] in fractionated total-body irradiation, p = 0.64), age (9% [21/241] inor = 40-year old-patients vs. 14% [9/64] in40-year-old patients, p = 0.29), sex (6% [7/113] in male patients vs. 12% [23/192] in female patients, p = 0.15), type of VOD prevention (16% [16/101] in patients using heparin vs. 10% [14/142] in those receiving dinoprostone and pentoxifylline combination, p = 0.23), type of bone-marrow transplantation (9% [10/108] in allogeneic bone-marrow transplantation group vs. 10% [20/197] in autologous bone-marrow transplantation group, p = 0.96), or type of acute leukemia (9.6% [13/135] in ALL vs. 10% [17/170] in ANLL, p = 0.93). However, VOD incidence was significantly lower in patients whose conditioning chemotherapy consisted of cyclophosphamide alone (6.5% [15/231] vs. 20% [15/74] by other drugs +/- cyclophosphamide, p0.0001), and in patients treated after 1985 (7% [16/226] vs. 18% [14/79] in those treated before 1985, p = 0.01). Multivariate logistic regression analysis revealed that the best independent factors influencing the occurrence of VOD were the male sex (p = 0.03), conditioning chemotherapy consisting of cyclophosphamide alone (p = 0.01), and bone-marrow transplantation after 1985 (p = 0.008).In our series of 305 acute leukemia patients treated with allogenic or autologous bone-marrow transplantation, total-body irradiation technique (fractionation or instantaneous dose rate) did not seem to influence the incidence of VOD.

Allogeneic BMT is presently recognized as one of the reference anti-leukemic treatments for AML patients. It could be a very useful therapy in CR1 AML if it is efficient as an early form of consolidation after induction therapy. Later procedures may be of lesser importance since they concern a population which may have already been cured by chemotherapy. Alternatively it is not solved if very early BMT gives patients sufficient therapy and provides lower toxicity. To answer this question we analyzed data from the Société Française de Greffe de Moelle (SFGM) on a sub-group of patients according to the following criteria: (1) Allogeneic BMT carried out on patients with AML in CR1; (2) after January 1985; (3) conditioning with CyTBI; (4) GVHD prophylaxis with MTX-CsA; (5) interval between diagnosis and BMT100 days. Forty-two fulfilled all criteria. Age was 31 +/- 8 years and M/F ratio was 19/23. WBC at diagnosis were 36 +/- 49 x 10(9)/l and four patients needed two induction courses to achieve CR1. Median follow-up is now 51 (24-116) months. Twenty-two patients developed a gradeor = 2 acute GVHD. Early transplant mortality at 1 year is no higher than 14%. Two patients died of secondary malignancies at 3.5 and 6.5 years after BMT. Finally 5-year (and 7-year) probabilities for relapse, survival, leukemia and event-free survival are respectively 17% (17%), 71% (62%), and 71% (71%) and 68% (59%). These data indicate the feasibility of such an approach with low mortality and low relapse rates providing a good long-term outcome. This should prompt an invitation to initiate the search for an HLA-identical sibling when AML is diagnosed in a young patient eligible for allo-BMT.

To evaluate the importance of fractionating total body irradiation (TBI) in patients receiving an allogenic bone marrow transplant (BMT) for an acute myeloblastic leukemia (AML) in first complete remission (CR1).Between 1983 and 1990, 171 consecutive patients received either single dose TBI (STBI) (n = 65) or fractionated TBI (FTBI) (n = 106) after being conditioned with cyclophosphamide and before receiving a non-T-depleted Human Leucocyte Antigen (HLA)-identical marrow. Both groups were comparable except for date of BMT and diagnosis-to-BMT interval (D-BMT).After 63 months median follow-up, transplant-related mortality (TRM), probability of relapse, and 5-year disease-free survival (DFS) were 0.38 and 0.27 (p = 0.04), 0.29 and 0.26 (p = 0.22), 0.43 and 0.56 (p = 0.06), respectively, for STBI and FTBI. The supposed influence of the schedule of TBI disappeared in the multivariate analysis: TRM was enhanced by severe acute graft vs. host disease (p = 0.0002), early years of transplant (before January 1, 1987) (p = 0.0003), and longer D-BMT intervals (p = 0.038). Relapse was linked to early years of transplant (p0.00001), and the absence of chronic GVHD (p = 0.007). Longer DFSs were observed for later years of transplant (after January 1, 1987 and later) (p = 0.001), milder acute GVHD (p = 0.005), and shorter D-BMT intervals (p = 0.045). Important improvements of the results were made during the 7-year observation period: TRM, probability of relapse, and DFS were, respectively, 0.36, 0.28, and 0.46 for patients transplanted before January 1, 1987 vs. 0.21, 0.15, and 0.67 after that date.Our data strongly suggest that allogenic BMT is the best postremission treatment for AML in CR1, and the results are better when BMT shortly follows the achievement of remission. The schedule of TBI was of little importance compared with the improvements made in the management of patients undergoing BMT during the 1980s, and, therefore, reports concerning data prior to 1985 should be interpreted cautiously.

Thirteen patients (pts) with highly refractory acute myeloid leukemia (AML) 10 pts with de novo AML and 3 with blast crisis of chronic myeloid leukemia were treated with carboplatin (CP) 150 mg/m2/day through continuous IV infusion for 7 consecutive days. Seven of them received CP at least as third or more line therapy after a median duration of the disease of 26 weeks. None achieved a complete remission but a good hematologic response, with disappearance of circulating blast cells along with correction of bone marrow failure, persisting for 3 months was obtained in one patient and correction of hyperbasophilemia was observed in another with blast crisis of chronic myelogenous. Myelosuppression was the most consistent toxic effect. Two deaths occurred, one from renal acute failure and the other from sepsis. Median survival after CP was 8 weeks (range 4 days-11 months) and the majority of patients were able to return home. When used as a single agent and with the dose-schedule used in this study, CP does not appear effective in refractory AML. Other studies are necessary to assess its role at an higher dose or in combination with other agents in earlier phases of the disease.

The authors studied the results of the arthroscopic treatment of the chronic calcifying tendinitis within a multi-center study of the French Society of Arthroscopy. 112 patients were available for the study. All shoulders had a preoperative radiographic clinical and radiographic evaluation. At follow up, functional results were assessed, using the Constant score, and X rays allowed to appreciate the acromial shape and the calcific deposit aspect. Several arthroscopic procedures were used on the calcification (respect or removal), and the coracoacromial arch (respect, ACL release or acromioplasty). This study found an objective success rate of 89 per cent and a patient subjective satisfaction rate of 82 per cent. Based on follow up radiographs, 88 per cent of the patients had a complete disappearance of the calcific deposit. There were no recurrence, no secondary rotator cuff tear. The results were not correlated with the age of the patients, or with the radiographic aspect (type, size, localization) of the calcification. The results were correlated with the arthroscopic procedure: they were better when the calcification had been removed (superior to deposit respect). Associated acromioplasty gave no better results: it was only considered as necessary when the calcification was not found (12 per cent). The greatest care must be taken in the surgical indication for this pathology because of a high rate of spontaneous resorption. The authors conclude that the arthroscopic surgery is a very effective method for chronic calcific tendinitis, compared to open procedure.

A functional assessment of fifty patients after ankle arthrodesis for post traumatic arthritis was carried out by means of an extensive clinical evaluation after an average follow-up of nine years. The data on position of ankle arthrodesis and gait analysis were examined to determine the effect of arthrodesis of the ankle on the subtalar and small joints of the foot. The Duquennoy point system was used to grade the ankle clinically and a new radiological method to determine the sagittal position of the ankle arthrodesis was developed. Equinus position was related with clinical damage on sub talar joint, and anterior cavus foot (92.8 per cent). This position was related with metatarsalgia in 26.9 per cent. Calcaneus position was related with posterior cavus foot (verticalization of the calcaneus). This position was related with the best functional results on walking, jumping and running.this study has showed that the ideal position of fusion of the ankle was neutral or slight flexion, slight valgus angulation of the hind part of the foot and 10 degrees of external rotation.

The authors have studied the result of endoscopic treatment in 129 non ruptured and non calcified tendinitis of the rotator cuff as well as 33 partial thickness tears included in a multicentric study made by the french arthroscopic society. The files included a revision form using Constant's functional evaluation and filled by a physician different from the operator, and a radiological standardized evaluation allowing to appreciate, from A.P. and lateral views, the acromion shape and the importance of the resection. From the analysis of our results it appears that acromioplasty associated with a section of the coraco-acromial ligament (C.A.L.) under arthroscopic control is very efficient in tears of the superficial, bursal face of the rotator cuff. The same did not apply to the tears of the deep, articular face, as their origin is probably different. In non ruptured and non calcified tendinitis, 90 per cent of our patients were subjectively better. According to Constant's index, we noticed 75 per cent of satisfactory results. The importance of acromioplasty was not related to good results. We therefore think that one should relativise the notion of impingement between the coraco-acromial arch and the tendons of the rotator cuff. Acromioplasty is only effective on one of the factors of tendinous pain. The improvement of our indication by a better knowledge of this pathology should allow us to improve the results of an endoscopic procedure which is now well known and whose advantages do not need to be demonstrated any more.

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.

Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I-endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2-dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells.

Adult T-cell leukaemia is the first blood disease caused by a retrovirus: HTLV-1. The authors report the first French series of 15 patients, of whom 9 came from the classical endemic areas--the Antilles and outer Caribbean Islands--and 6 from Africa where the serological prevalence of HTLV-1 is high but few cases of adult T-cell leukaemia have been reported. Emphasis is laid on the importance of immunodeficiency (refractory strongyloidiasis, Pneumocystis carinii pneumonia, polyclonal B lymphoproliferative syndrome) and of other pathologies associated with the retrovirus (polyarthritis, lymphocytic interstitial pneumonia). The authors also describe the presence of adenopathy in healthy carriers: either adenitis suggestive of retroviral infection, or Castelman's disease adenopathy. These clinical presentations are similar to those described in lymphadenopathy syndromes due to the human immunodeficiency viruses. Aggressive lymphomas require chemotherapy, but sooner or later resistance develops, and the prognosis is very poor. The indications for allogeneic bone marrow transplantation are still to be determined. The diagnosis of adult T-cell leukaemia must be considered in all patients with blood disease coming from the endemic areas.

A patient with aplastic anaemia, successively treated with caspofungin then liposomal amphotericin, developed a disseminated infection due to Acremonium, further confirmed as resistant in vitro to these drugs. Successful treatment was achieved with voriconazole. Multiple antifungal treatments may expose to the risk of breakthrough of multi-resistant pathogens in haematology patients.

Seventeen cases of Pseudomonas aeruginosa serotype O 16 septicaemia in patients with immune deficiencies are reported. All patients had a poor prognosis from the onset because of the advanced stage of their illness, the particular clinical form of their disease or because of the confirmed inefficacy of their anti-leukaemic chemotherapy. The neutrophil leukocyte count was less than 0.5 X 10(9)/l in all cases and 13 patients had also received wide-spectrum antibiotic therapy for at least 15 days. The septicaemia was accompanied by pelvic sepsis in 6 cases. The prognosis was very poor and 12 patients died rapidly in a state of shock. P. aeruginosa was an infrequent cause of infection during the 31 months period of observation but the O 16 serotype was the commonest in our department. The source of contamination seemed to be a chronic carrier state. P. aeruginosa is resistant to most of the antibiotics which would be expected to be effective.

In order to consolidate a complete or partial remission, 4 patients with T-cell malignancy received cyclophosphamide 120 mg/kg plus total body irradiation, followed by reinfusion of cryopreserved autologous bone marrow purged in vitro by the immunotoxin T 101 (SR 41322) composed of the murine monoclonal T 101 antibody coupled with the A chain of ricin. The immunotoxin was applied in doses of 10(-9) and 10(-8) M for periods of 4 and 20 hours at 37 degrees C. The recovery of CFUc and BFUe progenitors was total following incubation with IT 101, but reduced after cryopreservation (1-15 to 80% for CFUc,-33 to 47% for BFUe), haematopoietic recovery occurred within normal delays, demonstrating that autologous bone marrow pretreated with the immunotoxin can be successfully transplanted. However, the slow increase in lymphocytes and the occurrence of lethal infection in 2 cases indicate that an in-depth study of immunological reconstitution after in vitro treatment of bone marrow with ITT 101 is necessary.

Cryptosporidiosis may cause diarrhea after a conditioning regimen for allogeneic bone marrow transplantation. The case reported here suggests resurgence of latent cryptosporidiosis in early post-graft period, since other causes of immunosuppression such as graft-versus-host disease or transfusional LAV/HTLV III retroviral infection, were absent. The diagnosis was confirmed by rectal biopsy and ultrastructural analysis. Good response to spiramycin was obtained.

Clinical and histological findings of six patients with low grade non-Hodgkin lymphoma (NHL) which transformed to high grade tumours are reported: 5 out of the 6 cases showed transformation from the centroblastic-centrocytic type to the centroblastic-polymorphic type (Kiel classification). Clinical aggressivity, large tumour mass, high frequency of extranodal sites of disease, systemic symptoms and resistance to treatment were observed. This type of transformation is not rare, estimated to be about 20 p. 100 of cases in the literature, and is more common than Richter's syndrome in chronic lymphocytic leukaemia.

A case report is presented of a patient with a pleural effusion subsequently shown to have a localised immunoblastic lymphoma of the bronchus of non-Hodgkin's type. The development of this lymphoma in a patient with mycosis fungoides underlines the potential for the transformation of a T cell epidermoid lymphoma of low grade malignancy to a lymphoma of high grade malignancy.

Four men and four women, aged 16 to 43, developed dural sinus thrombosis, five patients with acute lymphoblastic leukemia (L.A.L.) and three with non Hodgkin malignant lymphoma (N.H.M.L.). All the cases of L.A.L. were F.A.B.-2 subtype without any unusual hematological features. In 6 cases, the disorders occurred during the phase of therapeutical induction (E.O.R.T.C.-A.L.L.-H.R. protocol) at D5, D10, D15, D26, D30, D38, and in 2 cases during maintenance after a period of remission. All patients had received Vincristine and Prednisone, intrathecal Methotrexate in 5 cases, encephalic irradiation in 3 cases and L-Asparaginase in one case. Three women were taking contraceptive drugs. The neurological symptoms and signs were headache due to intracranial hypertension in 6 cases, Grand Mal seizures in 5 cases, focal seizures in 2 cases, a regressive hemiparesis in 4 cases, stupor in 3 cases. CT scan was abnormal in 4 cases, displaying oedema in 3 cases and an hemorrhagic infarction in 1 case. Angiography showed in all cases occlusion of the superior sagittal sinus in 7 cases and of the transverse sinus on 1 case. Six patients received anticoagulant therapy. Outcome was fatal in 3 cases: in 2 cases of L.A.L., the condition worsened rapidly after the onset and death was related to a tentorial herniation; in 1 case of N.H.M.L. death resulted from an intercurrent infection.

Forty patients with refractory and/or relapsing acute leukaemia were treated with AMSA (90-120 mg/sq m/day) for 5 days combined with high dose cytosine-arabinoside (HDARAC) (3 g/sq m/12 hours) during the first 2 days. Complete remission was obtained in 46% of the 26 cases of acute myelogenous leukaemia, and the complete remission rate was fair (44%) in the 20 patients refractory to conventional induction treatments. The results were less satisfactory in the few patients with other cytological types: there were 2 complete remissions in 10 patients with acute lymphoblastic leukaemia and none in 4 patients with blast crisis of chronic myelocytic leukaemia. Haematological toxicity was severe, and 6 patients died during the aplastic phase. No cardiac toxicity associated with AMSA was observed, nor did the ocular, cutaneous or cerebellar side-effects described after longer courses of HDARAC develop. Complete remissions were relatively short, and 11 of 14 remitters relapsed after 2 to 11 months (median 4 months). However, 3 remitters underwent allogenic bone marrow transplantation with 2 surviving. Another patient has a prolonged fourth complete remission with AMSA + HDARAC maintenance treatment. It is concluded that the AMSA-HDARAC combination seems to be one of the best salvage induction regimens in acute myelogenous leukaemia.

Thirty-eight patients with haematological malignancies were treated with bone marrow transplantation using histocompatible immunotoxin T cell-depleted marrow siblings. All patients received conventional postgraft immunosuppression (methotrexate and/or cyclosporin A). Donor bone marrow was treated ex vivo with T101 Fab fragment coupled to ricin A-chain (T101 Fab-RTA) at a concentration of 10(-8) M of A-chain in association with NH4Cl (2 x 10(-2) M) in pH adjusted (7.8) incubation medium. A median cytoreduction of 99.5% (91-99.5) was obtained. The median of follow-up was 300 days. Only three patients developed grade II acute graft-versus-host disease (GVHD) (actuarial rate of acute GVHD: 9.1%). No chronic GVHD occurred. All patients but one engrafted. Six out of the 37 patients developed a documented bone marrow rejection (actuarial rate of graft failure: 18%). Ten patients relapsed (actuarial rate of relapse: 36.9%). These findings demonstrate that treatment of donor marrow with T101 Fab-RTA in association with NH4Cl at critical pH value can achieve a high level of mature T cell depletion and greatly reduce the incidence of bone marrow rejection and relapse after T cell-depleted allogeneic bone marrow transplantation.

Four patients with T-cell malignancies of poor prognosis (three with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia) received the following consolidation therapy for complete or partial remission: cyclophosphamide (120 mg/kg) plus total-body irradiation, followed by reinfusion of cryopreserved autologous marrow previously purged in vitro by immunotoxin T 101 (SR 41322). This immunotoxin is made of the murine monoclonal T 101 antibody coupled to chain A of ricin. The doses of immunotoxin used were 10(-9) and 10(-8) M, and the durations of incubation were 4 and 20 hours at 37 degrees C. Recovery of progenitors CFUc and BFUe was total following incubation with immunotoxin T 101, but diminished after cryopreservation (15%-80% for CFUc, 33%-47% for BFUe), suggesting an increased fragility of the incubated progenitors to freezing. In every case, hematopoietic recovery occurred within normal time periods, with a wbc count greater than 10(9)/L and a platelet count greater than 50 X 10(9)/L on Day 22 (range, 15-31) and Day 21 (range, 22-47), respectively, demonstrating the feasibility of autologous bone marrow transplantation with marrow pretreated by immunotoxin. However, the slow recovery of lymphocytes and the development of severe infections in two patients may indicate that an in-depth study of immunological reconstitution after in vitro treatment of the marrow with immunotoxin T 101 is necessary.