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Imatinib, approved more than 10 years ago, has significantly modified the natural history of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph ALL). In adults, 15–30% of patients wi...

Hyper acute and acute vascular rejections represent the major problem in organ xeno-transplantation. According to the humoral theory of transplantation, acute and chronic rejections of allografts a...

Stenotrophomonas maltophilia (Sm) pneumonia in immunocompromized hosts is an increasingly common nosocomial infection. Even though resistant to multiple antimicrobials, this gram-negative bacteria usually does not present with a fulminant course leading to a fatal hemorrhagic respiratory infection in neutropenic patients. We report here the case of a 63-year-old woman treated by intensive chemotherapy for acute myeloid leukemia (AML) who presented while severely neutropenic and thrombocytopenic a Sm pulmonary infection with hemoptysis leading to death in 48 h. The bronchoalveolar lavage (BAL) performed shortly before death was highly hemorrhagic and contained a striking amount of extra- and intra-cellular pathogens. Blood and BAL cultures grew S. maltophilia. Post-mortem examination revealed bilateral extensive intra-alveolar hemorrhage (IAH) associated with a great amount of microorganisms and severe bone marrow aplasia was observed without evidence of leukemia residual disease. Sm pneumonia usually does not evolve into such a devastating clinical picture although infections due to the bacteria are known to be associated with high morbidity and mortality. So far, the present observation is the fourth similar case reported in the literature. Even though an early diagnosis and an adequate antibiotic prescription may improve Sm infection prognosis, S. maltophilia proves difficult to eradicate due to a high resistance rate in part intrinsic but also in part acquired.

Out of 75 consecutive elderly AML patients who did not receive anti-leukemic treatment (52 pts) or failed to respond to differentiating agent (23 pts), 6 patients had survivals of 13.2 to 98 months with treatment restricted to supportive care. This cut-point is far longer than the median survival of the 235 elderly patients (3.5 mo.), either untreated (med. survival: 1 mo.) or treated (with treatment ranging from conventional induction to palliative chemotherapy) (4 mo.), admitted to our department within the same period of time. These cases of smoldering AML (4 women, 2 men) were all of AML2 FAB subtype (4 de novo, 2 post MDS) and presented with a significantly better performance status, lower WBC and circulating blast counts, higher platelet counts and with lower bone marrow infiltration than AML cases with more rapid progression. Cytogenetical analysis when available (3 pts) showed normal karyotypes and clonogenic assay performed in 3 of these patients showed a lack of (2 pts) or reduced in vitro leukemic cell growth (1 pt). The identification of specific characteristics of smoldering leukemia in the elderly might be an important development in the understanding of the physiopathology of acute leukemia and a tool for helping decision-making when selecting the time and intensity of cytotoxic treatment in these older patients.

Bladder cancer is the seventh most common cancer in men worldwide and accounts for approximately 5–10% of all malignancies among men in Europe. Superficial transitional cell carcinoma (TCC) represe...

To evaluate the frequency and the prognostic value of different mechanisms of drug resistance in acute leukemias, we investigated the expression of mdr1 by immunocytochemistry, mRNA slot blot or RT-PCR in 182 cases of adult acute myeloid and 37 cases of adult lymphoblastic leukemia. Before treatment, 39% of de novo AML, 38% of secondary AML, and 7% of de novo ALL exhibited a high level of mdr1 mRNA. After chemotherapy, the frequency of mdr1 gene expression in ALL raised dramatically to 60% (P0.005), while no significant change was found for AML cases. In 91 patients treated with MDR-related drugs, mdr1 gene expression was related to the failure of chemotherapy (P0.0001). The overexpression of multidrug resistance-associated protein (mrp) and anionic glutathione S-transferase (GST pi) was also investigated in 38 and 61 AML patients respectively. An overexpression of mrp gene was noted in 39% of the cases. For GST pi gene, the frequency of overexpression was 28%. A positive and significative correlation was found among mdr1, mrp and GST pi genes expression.

Prognostic factors in acute lymphoblastic leukemia (ALL) are used for treatment stratification of ALL. Definition of simple parameters such as the presence or absence of peripheral leukemic cells after one week of treatment could help for stratification. A retrospective study was conducted on 79 previously untreated adult patients with ALL followed in the Hematology department of Hotel Dieu from 1981 to 1991. 84% of patients achieved complete remission (CR), 7% were refractory to induction treatment, and 7 patients (9%) died during the first month after diagnosis. After multivariate analysis the only independent statistically significant factors for achieving CR were the absence of peripheral blast cells at day 7 (PBC D7) (p = 0.009) and age (50 years) (p = 0.03). For CR duration the same independent statistically significant factors were found (PBC D7 = 0 versus0, p = 0.008; and ageoror = 30 years, p = 0.045). The PBC D7 value was more significant when circulating blast cells were present at diagnosis. In patients with more than 50,000 PBC at diagnosis, the 10- years event free disease was 62% +/- 20% when PBC were absent at day 7 versus 0% when PBC were present (p0.002). All 20 patients with prolonged DFS had PBC D7 = 0 achieving CR by 28 days. The persistence of PBC at Day 7 could be used as a factor to identify a subgroup of poor prognosis adults with ALL.

In an attempt to improve the results of treatment in patients with relapsing or refractory acute myeloid leukemia (AML), we conducted a pilot study using a two-drug salvage regimen according to the in vitro clonogenic leukemic cell (CFU-L) drug sensitivity. Fourteen patients were included in the study, 10 with relapsing and 4 with refractory AML. Drug exposure was assessed for daunorubicin, cytosine arabinoside, etoposide, mitoxantrone and amsacrine. The two drugs with the best inhibitory effect on CFU-L were selected for the treatment. A complete remission was achieved in only 4 patients and a partial remission in 3 patients. Although the number of patients is too small for appropriate statistical analysis and for a definite conclusion to be drawn, the observed response rate with directed therapy did not appear better than that expected from empiric salvage regimen.

Twenty-two patients (mean age 41 years) in blast crisis or accelerated phase (AP) of chronic myelogenous leukemia (CML) were treated with cytosine arabinoside (Ara-C) 500 mg/m2 [intermediate dose] or 1000 mg/m2 [high dose] twice a day for 6 days and amsacrine (AMSA) 120 mg/m2 for 3 days. Twenty-one cases were of myeloid type and one was a lymphoid BC. The mean duration of aplasia (neutrophils0.5 x 10(9)/l) was 21.5 days. Four patients (18%) died of infection during aplasia and minor toxicities were noted for the remainders. Nine patients (41%) achieved a complete remission (CR) and 4 (18%) a partial response. Various additional therapies were proposed after induction treatment including allogeneic bone marrow transplantation (2 patients), Ara-C and AMSA maintenance or other regimens with or without alpha-interferon (9 patients). Median survival for the entire cohort was 20 weeks (wks), significantly superior for complete responders (37 wks) than for others (7 wks) (p = 0.008). In this study, age, sex, initial platelet or basophil counts, interval between diagnosis of CML and blast crisis were not predictive of response. Although inducing a high CR rate and associated with acceptable toxicity, this regimen did not improve the survival of patients with BC or CML, strengthening the need for alternate approaches to be defined.

Sequential evaluation of P-glycoprotein expression was performed in 29 patients with acute nonlymphoblastic leukemia using immunocytochemistry with the C219 antibody. At diagnosis, 32% of the patients exhibited more than 5% of the P-gp(+) leukemic cells. Under chemotherapy, 62% of the patients eventually expressed a subset of P-gp positive leukemic cells. After conventional doses of cytosine-arabinoside (Ara-C) and daunorubicin or mitoxantrone, positive P-gp cells were noted in 65% of the cases. This percentage was significantly higher (p = 0.002) than the proportion of positive cases (15%) observed after regimens containing either intermediate doses of Ara-C or cyclosporine A, a P-gp modulator.