In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P ¼ 0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (42 mg/kg) represented the major risk factor for bacteremia (P ¼ 0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.

Summary:Allogeneic hematopoietic stem cell transplantation is often used to treat hematologic malignancies. The efficacy of this procedure is due to both myeloablative conditioning and graft-versus-leukemia (GVL). However, the disadvantages of allogeneic transplantation include graft-versus-host disease (GVHD), relapse from the original tumor, and patient susceptibility to opportunistic infections. Lately, allogeneic transplantation has been developed to treat solid tumors, with the expectation that graft-versus-tumor (GVT), like GVL, will have a significant anti-tumor effect. This effect has been demonstrated in renal carcinomas, and with less evidence in breast cancers. Five patients with malignant ovarian tumors resistant to chemotherapy underwent allogeneic transplantation, four from bone marrow, and one from peripheral blood stem cells. All donors were HLA-identical siblings. One patient received a myeloablative conditioning regimen, while the other four received a non-myeloablative regimen. Two patients received donor lymphocyte infusions (DLI). Four of the patients presented with acute or chronic GVHD associated with tumor regression of at least 50%. These tumor regressions were measured by CA-125 levels and CT scans. The fifth patient died of rapid progression just after transplantation. Of the four transplantation survivors, three received a non-myeloablative regimen which did not seem to reduce treatment effectiveness. While it did reduce toxicity, one of these patients died of GVHD after 127 days. DLI was administered to two patients. These infusions seemed to promote GVHD which was able to control disease progression for one patient and had no apparent effect on the other. Allograft of hematopoietic stem cells might be of interest in ovarian cancer. The results in one patient also suggest that DLI may be an effective immunotherapy, although doses and timing need to be determined. The number of cases presented is small, however, and clinical experience on a larger scale will be required to determine the real clinical efficacy of graft versus cancerous ovarian cells.

Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered to 400-600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph þ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.

Summary:A 33-year-old woman developed progressive ovarian cancer resistant to classical chemotherapy agents. We performed a bone marrow allograft after a myeloablative regimen. During hematological recovery, she developed acute graft-versus-host disease (GVHD). From this time her tumor diminished progressively. One year post transplant she has limited chronic liver GVHD and is still free of disease. The complete remission of advanced ovarian cancer was probably related to the GVHD which might therefore provide a new treatment option for this disease. Bone Marrow Transplantation (2000) 25, 681-682. Keywords: ovarian cancer; allograft transplantation; graft-versus-host diseaseThe graft-versus-leukemia (GVL) effect has been reported in hematological malignancies after allogeneic treatments. This immunological effect has been recently described in patients with solid tumors after allogeneic bone marrow transplantation (graft-versus-tumor effect). 1-3 Ovarian carcinoma represents an additional target for this type of immunotherapy. 4 In this context, we report the first case of a patient who achieved a complete response after allogeneic bone marrow transplantation for ovarian cancer. Case reportA 33-year-old woman was diagnosed with ovarian cancer in May 1995. She presented with a serous papillary adenocarcinoma stage III C (FIGO). A partial remission was achieved after six chemotherapy courses (PAC: doxorubicin 240 mg total dose received (TDR), cyclophosphamide 6400 mg TDR, cisplatin 720 mg TDR). After this first-line chemotherapy complete surgery was performed, followed by intraperitoneal chemotherapy (doxorubicin 5 mg and cisplatin 25 mg once daily for 5 consecutive days). She relapsed 10 months later in September 1997. At this time she presented with an occlusive syndrome, subcutaneous tumor nodules and pulmonary metastases. This relapse was confirmed by an elevation of CA125 (164 U) and tomodensitometric examination. She was treated with seven courses of paclitaxel 1765 mg TDR and carboplatin 3140 mg TDR. A transitory partial response was obtained after four courses, but was followed by disease progression. According to our experience in autologous transplantation, the prognosis of the patient was poor and intensive chemotherapy followed by autologous peripheral blood stem cell transplantation was unlikely to be able to cure the disease. 5 Because of the good performance status of the patient, a bone marrow allograft was proposed with an HLA-identical, sex mismatched adult sibling.Before the allograft procedure the patient presented with abdominal tumor nodules, a progression of pulmonary metastatic lesions and the elevation of CA125 (169 U). The conditioning regimen consisted of myleran 4 mg/kg daily for 4 consecutive days and cyclophophamide 50 mg/kg daily for 4 consecutive days. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Complete hematological recovery was obtained, with full cytogenetic chimerism at day 30. Acute grade III GVHD (Glucksberg) involving the skin and...

Summary:graft contains monocytes which produce several cytokines including G-CSF. 6,7 Randomized studies have demonstrated that r-Hu G-CSF In this placebo-controlled randomized trial we evaluated the hematological and clinical effects of r-Hu GM-(recombinant human granulocyte colony-stimulating factor) or r-Hu GM-CSF (recombinant human granulocyte-macro-CSF after high-dose chemotherapy (HDC) followed by GM-CSF-mobilized PBPC transplantation. Fifty phage colony-stimulating factor) accelerate granulocyte recovery after bone marrow transplantation. [8][9][10][11][12] On the patients with poor prognosis malignancies were randomized in a double-blind study to receive either GMother hand, there are few and controversial reports concerning the efficiency of colony-stimulating factors (CSFs) on CSF or placebo after HDC followed by PBPC rescue. For all patients, PBPCs were recruited using a combithe hematological recovery and on the frequency of infectious complications after PBPC transplantation. [13][14][15][16][17][18] At the nation of VP-16 (300 mg/m 2 on days 1 and 2), cytoxan (3 g/m 2 on days 3 and 4) and GM-CSF (5 g/kg from present time, no randomized studies are available regarding the effect of GM-CSF after PBPC transplantation and retroday 5). No differences were demonstrated between the two groups in median time to neutrophil or platelet spective studies are few and not conclusive. 19In this unicenter placebo-controlled randomized trial we recoveries. There was no significant difference between the GM-CSF group and the placebo group in the investigate the effect of r-Hu GM-CSF after GM-CSF-mobilized PBPC transplant. We report neutrophil and platelet median duration of post-transplant hospitalization, in the number of days of antibiotic treatment, in the numrecoveries and related clinical parameters such as the number of febrile days, the rate of infections, the duration of ber of infections and in red blood cell or platelet transfusion requirements. There was a significant difference parenteral antibiotherapy and the time to discharge from hospital after PBPC transplantation. with an advantage for the placebo group in the mean duration of febrile days (P = 0.01). We conclude that the administration of GM-CSF in patients transplanted Patients and methods with GM-CSF-mobilized PBPC is not associated with a clinical benefit in term of tempo of engraftment, numInclusion criteria bers of documented infections, transfusion requirements and mucositis grading.