Biomedical subjects
Publications and source records attributed to G Damaj.
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.
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.
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.
Glanzmann's thrombasthenia is an autosomal recessive disorder characterized by a lack of platelet aggregation due to the absence of platelet glycoprotein IIb and IIIa. Usually, the disease leads to mild hemorrhage but sometimes bleeding is severe enough to be life-threatening. We report the case of a 16-year-old girl, presenting with very severe type 1 Glanzmann's thrombasthenia, successfully treated with an HLA-identical sibling bone marrow transplant (BMT). We also update the clinical and laboratory data of her brother, who had received a BMT 16 years ago for the same disease. In the light of these two cases and two others published in the literature, we discuss the indications for BMT from HLA-identical sibling donors in Glanzmann's thrombasthenia. Alloimmunization against the missing platelet GPIIb/IIIa complex and severity of bleeding episodes may constitute sufficient criteria for allogeneic BMT after careful assessment of the risk-benefit of such a procedure, although this remains exceptional in this disease. Bone Marrow Transplantation (2000) 25, 327-330.
Allogeneic bone marrow transplantation (BMT) is an effective treatment for Fanconi's anemia (FA) but it requires a dose reduction of alkylating agents used for conditioning because of the increased sensitivity of FA cells to DNA cross-linking agents. Oesophageal damage has not previously been described as a complication after allogeneic BMT for this indication. We report five cases of severe oesophagitis with stenosis in patients transplanted for FA. It occurred either early, or more surprisingly, several years after BMT and could have easily been misdiagnosed. It could be explained by hypersensitivity of the FA mucosal cells to cytotoxic agents despite the reduced doses of cyclophosphamide and irradiation or to non diagnosed congenital abnormalities of the oesophagogastric junction. However, the evolution of the oesophageal disease was favorable in all, and none of the patients developed secondary cancer. Awareness of this complication will lead to earlier diagnosis and treatment of oesophageal stenosis and related malnutrition.
PURPOSE: To identify predictive factors of survival, relapse, and transplantation-related mortality (TRM) among patients with therapy-related myelodysplastic syndrome (t-MDS) or acute leukemia (t-AML) who underwent allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From 1980 to 1998, 70 patients underwent allogeneic BMT for t-MDS (n = 31) or t-AML (n = 39) after prior cytotoxic exposure. Thirty-three patients had received induction-type chemotherapy before BMT. At the time of transplantation, there were 24 patients in complete remission (CR) and 46 with active disease. RESULTS: With a median follow-up of 7.9 years (range, 1.1 to 18.8 years) after BMT, 16 patients are alive, whereas 19 died of relapse, 34 of TRM, and one of relapse of the primary disease. The estimated 2-year overall survival, event-free survival, relapse, and TRM rates were 30% (95% confidence interval [CI], 19% to 40%), 28% (95% CI, 18% to 39%), 42% (95% CI, 26% to 57%), and 49% (95% CI, 36% to 62%), respectively. In multivariable analysis, age greater than 37 years, male sex, positive recipient cytomegalovirus (CMV) serology, absence of CR at BMT, and intensive schedules used for conditioning were associated with poor outcome. CONCLUSION: BMT is an effective treatment for patients with t-MDS or t-AML who have responsive disease and, in particular, who have no poor-risk cytogenetic features. The poor results of the other patients, especially those with active disease at BMT, emphasize the need to delineate indications and perform prospective protocols.
Human herpes virus 8 (HHV8) may be sexually transmitted, but transmission via blood cells has not yet been excluded. We used a modified immunofluorescence assay to detect Ab to HHV8 latency-associated nuclear Ag in sera of 200 allogeneic BMT recipients and their related donors. In control subjects, Ab were found in 85% of patients with AIDS-related Kaposi sarcoma (n = 52), 34% of HIV-1 infected subjects without Kaposi sarcoma (n = 56) and 9. 5% of blood donors (n = 42). Among BMT donors, 14.5% were HHV8+, while 10% of recipients were positive before, and 18% after BMT. In the 176 HHV8-negative recipients at BMT, there was no relationship between post-BMT seroconversion, which occurred in 26 cases (15%), and the donor's serological status. Of note, 10 HHV8+ recipients before BMT became negative post-BMT. Outcome of BMT was not influenced by prior HHV8 seropositivity, seroconversion or seroreversion of recipients. That HHV8 seropositivity among blood donors from the Paris area was comparable to that of BMT donors and recipients before BMT indicates that these patients had not been at risk of HHV8 by blood products received before BMT, although post-BMT HHV8 seroconversion probably corresponded to contamination by blood transfusions rather than by the BMT.
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We report one patient with paralysis of the right upper extremity, bilateral cerebellar syndrome, and cognitive changes after treatment with interleukin-2 for metastatic renal cell carcinoma. Focal neurologic disturbances were associated with multiple images of cerebral infarcts but also with extraneurologic signs and autoantibodies. We suggest that this is a case of cerebral vasculitis with an autoimmune mechanism triggered by interleukin-2 therapy.