The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921).

This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor.     

P-glycoprotein positive, drug resistant invasive lymphoepithelial thymoma: treatment response to chemotherapy with cyclosporin and quinine.

A case of invasive drug resistant thymoma, expressing P-glycoprotein, which showed noticeable clinical response to chemotherapy and the multidrug resistance modulating agents cyclosporin and quinine is reported. A 46 year old man presented with severe left shoulder pain and a diagnosis of invasive lymphoepithelial thymoma was made following chest x ray and a computed tomography scan. The patient underwent extensive chemotherapy without resolution of the tumour. More than 90% of the malignant epithelial cells were strongly positive for P-glycoprotein and based on this observation, cyclosporin and quinine were added to the chemotherapy regimen. The mediastinal mass completely resolved and the size of the pleural metastasis decreased substantially. The patient, however, died of an intercurrent infection. This case report highlights the feasibility and efficacy of using cyclosporin and quinine in combination with VAD chemotherapy in the treatment of invasive thymoma.     

MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies of 11q23

We here report the clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data on 14 patients with a myeloid malignancy and structural aberration of chromosome band 11q23 associated with overrepresentation or amplification of the MLL gene. The number of copies of MLL varied from three (two cases) to a cluster consisting of multiple hybridization spots. Together with previous reports, available data indicate that amplification of 11q23/MLL is a recurrent genetic change in myeloid malignancy. It affects mainly elderly patients and is often associated with dysplastic bone marrow changes or with complex karyotypic aberrations, suggestive of genotoxic exposure. It is associated with a poor prognosis. In addition, FISH analysis of nine cases with additional 11q probes showed that the overrepresented chromosomal region is generally not restricted to MLL, and Southern blot analysis indicated that amplification does not involve a rearranged copy of this gene. The significance of MLL amplification and the mechanisms by which it could play a role in leukemogenesis and/or disease progression remain to be elucidated.     

Bilateral granulomatous panuveitis as initial presentation of diffuse systemic T cell lymphoma.

A high-grade diffuse T cell lymphoma, initially simulating bilateral panuveitis, was diagnosed by analysis of a vitreous biopsy specimen and a breast tumor in a 57-year-old woman. It responded favorably to aggressive chemotherapy before it relapsed in leukemic transformation. This case emphasizes the misleading initial symptoms of primary intraocular lymphoma and the role of immunophenotyping in the diagnosis and classification of lymphoproliferative ocular disorders. The presentation and management of uveal lymphoid neoplasia are discussed.     

Sustained clinical response of large hepatocellular carcinoma after chemoembolization with pirarubicin, amiodarone and Lipiodol

Although chemoembolization is known to be an effective palliative treatment in hepatocellular carcinoma, it has a limited effect in large tumors. We report the case of a patient with a large hepatocellular carcinoma of the left liver who had a significant and sustained clinical response after six sessions of chemoembolization with a pirarubicin/amiodarone/lipiodol emulsion. Pirarubicin is an anthracycline which penetrates faster than doxorubicin into cancer cells. Amiodarone is a multidrug resistance inhibitor. Polysorbate 80, an excipient of injectable amiodarone stabilizes the anthracycline/lipiodol emulsion. The clinical efficacy of this new formulation could be evaluated in a phase II clinical trial.     

2-Chlorodeoxyadenosine with or without daunorubicin in relapsed or refractory acute myeloid leukemia

 2-Chlorodeoxyadenosine (2-CdA) is a purine analogue which has proved to be active in acute myeloid leukemia (AML), especially in children. In adults, results yielded by 2-CdA alone or with ara-C were less encouraging. Here we report on the efficacy of 2-CdA with or without daunorubicin (DNR) in 19 relapsing or refractory adult AML patients, with a median age of 57 years. 2-CdA was administered as a continuous infusion to all patients at a dose of 0.1 mg/kg per day for 7 days. For 14 patients, DNR was added at a dose of 50 mg/m² per day on days 5, 6, and 7. Antileukemic activity was observed in all the patients, but no single complete remission was achieved. One patient had a long-lasting partial response (response rate=5%). The remaining patients died of progressive AML (n=7), uncontrollable infection with persistent disease (n=10), and cerebral hemorrhage (n=1). Median survival from start of 2-CdA therapy was 56 days. Long-lasting neutropenia and transfusion-dependent thrombopenia were encountered in all 16 evaluable patients. Grade 4 hepatic toxicity occurred in one patient. Other side effects included nausea in six, mucositis in three, and mental disturbances in three patients. Compared with 2-CdA alone, the addition of DNR to 2-CdA changed neither the response rate nor the toxicities. In conclusion, our data do not support the use of 2-CdA ± DNR for relapsing or refractory adult AML patients, at least as used in the present regimen. Received: 21 July 1997 / Accepted: 18 November 1997     

Acute lymphoblastic leukemia in the elderly

We report our findings in 18 patients with acute lymphoblastic leukemia (ALL) aged 60 years or older. A preleukemic syndrome was observed in 2 patients. Compared to younger adults with ALL, L3 morphology was unexpectedly frequent (4/16). T-ALL was not observed. Other criteria of poor prognosis (high white blood cell count, CNS involvement, organomegaly, high serum LDH) were similar to those reported in young adults. 12 patients were treated with an OPAL-derived regimen, 4 with the MAV regimen, 1 with vincristine and prednisone, 1 with 6-mercaptopurine. Complete remission was achieved in 8 patients but proved short-lived. 5 patients died in aplasia and 5 failed to achieve remission. Median survival for the whole group was 3 months. ALL in the elderly raises the dilemma of an aggressive disease in patients with poor tolerance to intensive therapy.     

Recommendations in the event of a suspected transfusion-related acute lung injury (TRALI)

The following recommendations, which aim at improving the clinical diagnosis ofTRALI and the laboratory investigations that can support it, were drawn up by a working group of the Superior Health Council. TRALI is a complication of blood transfusion that is both serious and underreported. Systematic reporting may help to develop preventive actions. Therefore, the Superior Health Council recommends that there should be a more stringent surveillance of patients who receive a blood component transfusion. The clinician should pay very close attention to any change in the patient's respiratory status (cf. dyspnoea and arterial desaturation), which should be notified systematically to the haemovigilance contact person in the hospital.     

Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission

To evaluate factors influencing outcome and incidence of long-term complications, we analyzed, in a retrospective, multicenter study, 387 children who underwent autologous hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) in first complete remission (CR). Median follow-up time from transplantation was 60 months. Transplantation of bone marrow cells was performed in 318 children, whereas in 60 patients peripheral blood progenitor cells (PBPCs) were used. In multivariate analysis, we investigated the variables influencing probability of hematopoietic recovery, transplantation-related mortality (TRM), relapse, and leukemia-free survival (LFS). We found that use of PBPCs as stem cell sources and use of BCNU (N,N-bis[2-chloroethyl]-N-nitrosourea), amsacrine, VP-16, and cytosine arabinoside (BAVC) as a preparative regimen were associated with faster neutrophil recovery. Infusion of PBPCs, young age of patients, use of BAVCs, and absence of marrow purging predicted an accelerated platelet reconstitution. The 5-year Kaplan-Meier estimates of TRM, relapse, and LFS were 3% +/- 1%, 39% +/- 3% and 60% +/- 3%, respectively. Relapse probability was increased in children given the BAVC regimen, and it was decreased after in vitro purging of hematopoietic progenitors and in children with a French-American-British classification of M3 and a time interval of 170 days or more between CR and HSCT. These 2 latter variables favorably influenced the probability of LFS, which was, by contrast, reduced with the BAVC regimen. Thirty-three percent of patients surviving more than 18 months experienced at least one late sequela; use of total body irradiation was the only predictive factor. The results obtained in this analysis can be of help in designing prospective studies of autologous HSCT in children with AML in first CR.