Nadine Morineau

Longitudinal Study of Bacterial, Viral, and Fungal Infections in Adult Recipients of Bone Marrow Transplants

The epidemiology of infections was studied in a retrospective cohort of 446 recipients of bone marrow transplants (BMTs; 92 of which were allogeneic and 354 of which were autologous) during 1993--1996. Infections that were microbiologically documented in 274 recipients included bacteremia, urinary tract infections, cytomegalovirus viremia, fungemia, invasive aspergillosis, and catheter-related infections. During the period of neutropenia, no differences were found between recipients of allogeneic BMTs and recipients of autologous BMTs with regard to the incidence and the nature of infection. After patients underwent engraftment, bacteremia, cytomegalovirus viremia, and invasive aspergillosis were significantly more common in recipients of allogeneic BMTs than in recipients of autologous BMTs. Deaths caused by infection were uncommon and were mainly the result of invasive aspergillosis. Therefore, empirical antimicrobial therapy should be the same for recipients of both allogeneic and autologous BMTs during the period of neutropenia; after engraftment, more attention should be paid to the risk of infection in allogeneic BMT recipients, particularly with regard to detection and prevention of invasive aspergillosis.

Zygomycosis after Prolonged Use of Voriconazole in Immunocompromised Patients with Hematologic Disease: Attention Required

We describe 4 cases of zygomycosis that occurred after prolonged use of voriconazole in severely immunocompromised patients with hematologic disease. An invasive infection was present in 3 patients who died soon after the diagnosis at 12, 13, and 45 days. Physicians should be mindful of this potential risk after treatment with voriconazole.

High incidence of cryptic translocations involving the Ig heavy chain gene in multiple myeloma, as shown by fluorescence in situ hybridization.

Cytogenetic studies have shown rearrangements of the Ig heavy chain (IGH) gene at 14q32 in 10–60% of patients with multiple myeloma (MM) or primary plasma cell leukemia (PCL). Analysis of MM patients and human myeloma cell lines (HMCL) using interphase fluorescence in situ hybridization (FISH) and molecular techniques has shown IGH rearrangements in 75% of MM cases and in up to 100% of HMCL. A review of the literature revealed at least 18 different partner chromosomal regions. To investigate whether some of these translocations were recurrent and possibly to identify new partner regions, we developed a set of FISH probes to detect every IGH recombination. We analyzed 28 MM and 4 primary PCL patients with abnormal karyotypes and 12 HMCL. Whereas conventional cytogenetics detected a 14q32 abnormality in only 15% of the patients, FISH detected it in 47% of patients and in 75% of HMCL. The partner chromosome was identified in 10 of 15 patients with a 14q32 rearrangement. Interestingly, the same t(4;14)(p16;q32) was detected in five patients and three HMCL, i.e., 33% of patients and HMCL with an IGH rearrangement. New partner chromosomal regions have also been identified, i.e., 9p13, 12p11, 12p13, and Xq28, besides the previously reported 8q24, 11q13, 12q24, and 16q24 rearrangements. The genes involved in these new translocations are not known, except for 9p13, where PAX5 was shown to be the partner gene. We conclude that: 1) IGH recombinations are frequent but not constant in MM, 2) these rearrangements often occur through cryptic translocations, and 3) the t(4;14)(p16;q32) is one of the most frequent translocations, but many other chromosomal regions may be involved. Genes Chromosomes Cancer 24:9–15, 1999.

A combination of anti-interleukin 6 murine monoclonal antibody with dexamethasone and high-dose melphalan induces high complete response rates in advanced multiple myeloma.

To improve the complete response (CR) rate in advanced multiple myeloma (MM) without increasing the toxicity of high‐dose therapy, we have used a new conditioning regimen. A combination of BE‐8 [an anti‐interleukin 6 (IL‐6) murine monoclonal antibody] and dexamethasone followed by high‐dose melphalan (220 mg/m2) and autologous stem cell transplantation was used to treat a series of 16 patients with advanced multiple myeloma. A strong inhibition of IL‐6 activity evaluated by quantification of C‐reactive protein was observed in all patients and was correlated with the high CR rate achieved with this combination therapy.

P53 deletion is not a frequent event in multiple myeloma

Recently a high incidence of interstitial deletion of the P53 locus has been reported in multiple myeloma (MM) patients. Considering the importance of such an event, we analysed 79 patients with advanced‐stage disease using fluorescence in situ hybridization (FISH). Strikingly, we found only 7/79 patients with a P53 deletion. In order to rule out any differences in probe selection, we reanalysed all the patients with the same probe as that used in a previous study, and confirmed the low incidence of P53 deletion (7/79, 9%). The only explanation is a difference in hybridization efficiency. Since hybridization is far less efficient on malignant plasma cells than on other bone marrow cells we suggest that this poor hybridization efficiency may lead to a false P53 deletion.

18F-fluorodeoxyglucose–positron emission tomography before, during and after treatment in mature T/NK lymphomas: a study from the GOELAMS group

BACKGROUND In non-cutaneous T-cell/natural killer (T/NK) lymphomas, the prognostic value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) during or after therapy is unknown. PATIENTS AND METHODS In this retrospective study, 54 T/NK lymphoma patients were assessed using FDG-PET before (n = 40), during (n = 44) and/or after therapy (n = 31). RESULTS FDG-PET showed an abnormal FDG uptake in all cases. Interim FDG-PET was negative in 25 of 44 cases. After completion of therapy, 19 of 31 patients reached complete remission with negative FDG-PET. In ALK+ anaplastic large cell lymphomas, the 4-year progression-free survival (PFS) was 80% and the negative predictive value of post-therapy FDG-PET was 83% (n = 9). In ALK- T/NK lymphomas, the 4-year PFS was 59% for patients with a negative interim FDG-PET versus 46% for patients with a positive interim FDG-PET (P = 0.28, n = 35). Similarly, there was no statistical difference in 4-year PFS between negative and positive post-therapy FDG-PET in these lymphomas (51% and 67%, respectively, P = 0.96). The 4-year cumulative incidence of relapse from a negative post-therapy FDG-PET was 53% in ALK- T/NK lymphomas. CONCLUSIONS Although T/NK lymphomas are FDG-avid at diagnosis, a negative interim or post-therapy FDG-PET does not translate into an improved PFS in ALK- T/NK lymphomas.

Disseminated mucormycosis associated with invasive pulmonary aspergillosis in a patient treated for post-transplant high-grade non-Hodgkin's lymphoma

The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkins lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed.

Ostéoarthrite à Pseudallescheria boydii chez un patient porteur de leucémie aiguë lymphoblastique : à propos d'un cas

Pseudallescheria boydii arthritis in a patient with acute lymphoblastic leukemia: a case report. Introduction. — The outcome of neutropenic patients with Pseudallescheria boydii infection is poor. Exegesis. — We report the first case of Pseudallescheria boydii hip arthritis in a patient treated for acute lymphoblastic leukemia. In vitro susceptibility testing showed that the strain was resistant to amphotericin B, fluorocytosine and nystatin, but susceptible to itraconazole. The patient received oral itraconazole (600 mg/day) and clinical symptoms initially resolved. Two months later, after a course of chemotherapy and high-dose steroids while receiving oral itraconazole treatment, the patient developed fever, skin lesions and disseminated lung infiltrates due to Pseudallescheria boydii and finally died. Conclusion. — This case illustrates the severity of fungal infections due to Pseudallescheria boydii despite a presumably well-conducted antifungal therapy.

Early Intensive Therapy with Autologous Stem Cell Transplantation in High-Risk Hodgkin's Disease: Long-Term Follow-Up in 35 Cases

Thirty-five adult patients with high-risk HD (HD) defined by (1) Ann Arbor stage IV or bulky nodal disease (tumor/thorax ratio > 0.45) and (2) no or partial response (PR) (< 75%) to the initial 3 courses of ABVD, received an early intensive therapy with autologous stem cell transplantation (ASCT). Thirty patients were considered as partial responders and 5 as refractory to initial chemotherapy. Conditioning regimen consisted of chemotherapy alone (CBV in 11 patients before 1993, BEAM in 13 patients since 1993) followed by adjuvant radiotherapy: 40 Gy) on the initial sites of bulky disease, or 12 Gy total body irradiation plus 120 mg/kg cyclophosphamide in 11 patients with disseminated extra-nodal disease. All 30 patients in PR at the time of ASCT experienced prolonged complete remission (CR). One patient died in CR from an acute myocardial infarction 48 months after ASCT. Four out of the 5 patients with refractory disease at the time of ASCT experienced rapid progression of HD leading to death in 3 cases. After 6 years of CR post-ASCT, the last refractory patient died of myelodysplastic syndrome diagnosed 2 years after intensive therapy. With a median follow-up for surviving patients of 51 months (range: 11-111), the cumulative probability of 8-year overall survival is 75.6% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). The cumulative probability of 8-year event-free survival is 79.9% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). We conclude that early intensive therapy with ASCT is feasible in patients with high-risk HD and induces a high cure rate in chemosensitive patients. In primary refractory patients, new therapeutic approaches are warranted.

A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first line treatment of older patients with mantle cell lymphoma

We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P<0.0001). Neither the mantle cell lymphoma index, nor fluorodeoxyglucose-positron emission tomography nor Ki67 positivity (cut off of ≥30%) showed a prognostic impact for survival. Hematologic grade 3-4 toxicities were mainly neutropenia (51%), thrombocytopenia (35%) and lymphopenia (65%). Grade 3-4 non-hematologic toxicities were mainly fatigue (18.5%), neuropathy (15%) and infections. In conclusion, the tested treatment regimen is active as frontline therapy in older patients with mantle cell lymphoma, with manageable toxicity. Minimal residual disease status after induction could serve as an early predictor of survival in mantle cell lymphoma. ClinicalTrials.gov: NCT 01457144.