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We evaluated early and late hematopoietic reconstitution in 27 patients with advanced lymphoma, Hodgkin’s disease, and breast or ovarian cancer after treatment using high-dose/myeloablative conditioning regimens and autologous peripheral blood stem cell (PBSC) transplantation. Eighteen patients (67%) received G-CSF 5 μ g/kg/day following chemotherapy and nine (33%) were mobilized using G-CSF alone. Each patient had 7 × 108 mononuclear cells (MNC) per kg collected. G-CSF was administered post-PBSC infusion. While all patients showed prompt granulocyte recovery by day 14, platelet recovery failed to occur in four (15%) heavily pretreated patients with non-Hodgkin’s lymphoma. Retrospective analysis in 17 patients revealed that the infused number of CD34 surface antigen-positive cells correlated with time to granulocyte (r = 0.59, P = 0.012) and platelet (r = 0.58, P = 0.021) recovery. Patients receiving the higher numbers of CD34+ cells had consistently better hematologic parameters at all times examined. At 180 days post-transplant, the median Hb level was 124 g/l vs 88 g/l (P = 0.004); platelet count was 202 × 109/l vs 25 × 109/l (P = 0.004); and neutrophil count was 3100 × 106/l vs 1400 × 106/l (P = 0.15). Hemoglobin strongly correlated with the CD34+ cell dose at 360 days (r = 0.90, P = 0.01). We conclude that graft CD34+ cell content appears to be an indicator of the quality of late as well as early hematopoietic function. [ABSTRACT FROM AUTHOR]

The combination of busulfan and cyclophosphamide has seldom been employed as a conditioning regimen for patients with lymphoma. Twenty patients with relapsed or refractory lymphoma were treated with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BU/CY) followed by peripheral blood stem cell rescue in 19 patients or autologous bone marrow in one patient. There were 12 females and eight males, with a median age of 48 years (range 30–65). Four patients had Hodgkin’s disease, and 16 patients had non-Hodgkin’s lymphoma. Disease status at the time of BU/CY was: first relapse in 10 patients (four patients with chemosensitive disease and six patients with chemoresistant disease), primary refractory disease in six patients, and more advanced disease in four patients. Excessive treatment-related toxicity was not noted. There were no cases of interstitial pneumonitis, but three cases of veno-occlusive disease occurred. At 2 years, the estimated overall survival and event-free survival are 50% and 33%. We concluded that BU/CY seems to have sufficient anti- lymphoma activity, is devoid of excessive toxicity and warrants further investigation in this patient population. [ABSTRACT FROM AUTHOR]

The article presents a study on the use of sirolimus to prevent leukemias and lymphomas in T-cell replete transplantations from haplotype-mismatched donors. Seventeen patients are tracked, who all underwent transplants and lists survival rates and causes of death. The authors claim that sirolimus should be a primary immunosuppressive to prevent tumors in these cases.

There is little data comparing the activity and toxicity of donor lymphocyte therapy with granulocyte (G)-CSF-mobilized cells (G-donor lymphocyte infusion (DLI)) with the conventionally collected DLI (C-DLI) after allogeneic blood or marrow transplantation. We retrospectively evaluated 67 patients to compare the efficacy and toxicity of GCSF-mobilized DLI with C-DLI in the treatment of relapse of malignant disease or poor donor engraftment post transplant. We assessed clinical outcomes that may represent the immunological outcome of DLI. The median OS was 210 days (range 3-2436 days), 291 days (range 17-1491 days) in the G-DLI group (15 patients) and 207.5 days (range 3-2436 days) in the C-DLI group (52 patients). The median PFS time was 72 days (range 8-1491 days) in the G-DLI group vs 82 days (range 1-2436 days) in the C-DLI group. Rates of post DLI GVHD and improvement in donor engraftment were similar in the G-DLI and C-DLI groups. We conclude that G-DLI appears to have similar therapeutic activity to that seen with C-DLI, and where such cells are available they may be substituted for conventional donor lymphocytes. [ABSTRACT FROM AUTHOR]

High-dose melphalan is considered the current standard of care among the preparative regimens used in peripheral blood autologous SCT (ASCT) for multiple myeloma (MM). We report the results of a single ASCT in 79 MM patients using the BU/CY conditioning regimen, with BU 1 mg/kg p.o. or 0.8 mg/kg i.v. every 6 h × 16 doses, and CY 60 mg/kg per day i.v. for 2 days. ASCT was carried out in first (62%) or subsequent remission/refractory disease (38%). For an overall RR of 86%, 48 and 20 patients achieved PR and CR, respectively. At a median follow-up of 41 months (range 2–132 months), the estimated median OS and PFS were 45 months (95% confidence interval (CI)=38–92) and 20 months (95% CI=15–25), respectively. The BU/CY regimen was well tolerated, and transplant-related mortality was 4%. Clinical outcomes of the BU/CY regimen are not superior to those obtained in historical controls with high-dose melphalan followed by a single ASCT. Therefore, considering even the greater complexity of administration of the BU/CY regimen compared with that of single-agent melphalan, we believe the latter should remain the conditioning regimen of choice for ASCT in MM.Bone Marrow Transplantation (2009) 44, 157–161; doi:10.1038/bmt.2008.446; published online 9 February 2009 [ABSTRACT FROM AUTHOR]

A multistep HDC regimen was designed as first-line chemotherapy for MBC. Twenty-four patients with MBC and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (5000 mg/m²), and etoposide (1000 mg/m²) (CyVP16), followed by granulocyte colony-stimulating factor (GCSF). Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m²), thiotepa (500 mg/m²) and carboplatin (800 mg/m²) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastrointestinal toxicity three cycles of doxorubicin (50 mg/m²) and taxol (150mg/m²) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia. Patients received CTCb 32 days after starting CyVPI6. After CTCb the median number of days to ANC >5 x 10[sup9]/1 was 10 and to a platelet count >20 x 10[sup9]/1 was 14. Neutropenic fevers developed in 16 patients. There were no hemorrhagic episodes. A total of 69 cycles of doxorubicin and taxol were delivered (87% of planned). The median time from PBSC infusion to the first cycle was 38 days. The median time to the second cycle was 27 days and to the last cycle was 24 days. One patient developed congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible with acceptable toxicity. [ABSTRACT FROM AUTHOR]

A 32-year-old male received an allogeneic peripheral blood stem cell transplant (alloPBSCT) for myelodysplasia from his one HLA-A antigen mismatched brother. He is alive with trilineage engraftment and without active GVHD 200 days after transplant. In July 1986 he underwent orthotopic cardiac transplantation for viral cardiomyopathy and has received continuous immunosuppressive therapy. A post-transplant lymphoproliferative disorder with Hodgkin-like histopathology was diagnosed in August 1993 and was successfully treated with four cycles of MOPP chemotherapy. Due to persistent pancytopenia he underwent a bone marrow aspiration and biopsy in May 1996 which revealed monosomy 7 and morphologic changes compatible with myelodysplasia. This is the first report of a cardiac transplant recipient receiving an allogeneic hematopoietic stem cell transplant. [ABSTRACT FROM AUTHOR]