No abstract available.
Busulfan* ; Lung*

With the development of chemotherapeutic agents and bone marrow transplantation, high dose conditioning chemotherapy before bone marrow transplantation, such as busulphan, have become more widely used. Of the side effects following chemotherapy, the cutaneous side effects of hair loss occur in high incidence. Alopecia following chemotherapy was generally known to recover completely in spite of subtle changes to the hair shaft. However, we recently experienced five cases of permanent incomplete regrowth of hair after cessation of conventional chemotherapy or high dose conditioning chemotherapy. In Korea, permenant alopecia following chemotherapy has not yet been reported and we reviewed them with the possible risk factors such as duration and kind of chemotherapeutic agents.
Alopecia* ; Bone Marrow Transplantation ; Busulfan ; Drug Therapy* ; Hair ; Incidence ; Korea ; Risk Factors

No abstract available.
Animals ; Busulfan* ; Fetal Blood* ; Humans* ; Infant, Newborn* ; Liver* ; Mice* ; Umbilical Cord*

OBJECTIVETo evaluate the long-term outcome of 60 leukemia patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) prepared with busulphan-cyclophosphamide (BU-CTX(2)) conditioning regimen.

METHODSFrom April 1994 to August 2000, 60 leukemia patients (35 male, 25 female; median age 32 years old), including 20 acute myeloid leukemia (AML, CR(1) n = 19, CR(2) n = 1), 15 acute lymphocytic leukemia (ALL, CR(1) n = 8, CR(2) n = 6, CR(3) n = 1), and 25 chronic myeloid leukemia (CML, CP(1) n = 24, CP(2) n = 1) received allogeneic hematopoietic stem cells from HLA-identical siblings (n = 53), 1-locus mismatched siblings (n = 4), or HLA-identical unrelated donor (n = 3). BU-CTX(2) was used as conditioning regimen. All patients received cyclosporine A and either methotrexate (n = 54) or methylprednisolone (n = 6) for graft-versus-host disease (GVHD) prophylaxis.

RESULTSAll 60 patients got sustained engraftment. Acute GVHD (aGVHD) occurred in 22 patients (36.7%), while the incidence of aGVHD was 48.0% for the CML, 30.0% for the AML and 26.7% for the ALL patients. Thirty-eight patients are still alive in complete remission with a median follow-up of 30 (12 approximately 84) months and 22 died. The main causes of death were aGVHD in 3, CMV-IP in 7, and relapse in 11 patients. The remaining one died of pulmonary infection. Among 11 patients who died of relapse, 8 were ALL relapsed in the early posttransplant stage. All 4 long-term survivors of ALL developed chronic GVHD. The probability of DFS at 3 year for CML, AML and ALL patients was 80.0%, 70.0% and 26.7%, respectively.

CONCLUSIONBU-CTX(2) is an effective conditioning regimen for patients with AML and CML, resulting in a low relapse and high long-term survival rate. However, it is not effective enough for patients with ALL, because of a higher incidence of relapse.

There have been few cases of Neurofibromatosis associated with Chronic Myelocytic Leukemia in literature and we found only one report in Korea which described the association of Chronic Myelocytic Leukemia with Neurofibromatosis. We report a case of patient whose clinical and hematological findings were compatible with Chronic Myelocytic Leukemia and Neurofibromatosis. Busulfan was used in the treatment of this patient followed by some degree of remission. A brief review of literature supporting our diagnosis was included in this report.
Busulfan ; Diagnosis ; Humans ; Korea ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Neurofibromatoses*

OBJECTIVETo retrospectively analyze the safety and efficacy of busulfan (BU) combined with cyclophosphamide (CY) as the conditioning regimen of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM).

METHODSThe safety and efficacy of the BUCY regimen were evaluated through observing the adverse reactions, recovery of hematopoietic reconstitution, response and survival in 20 patients after auto-HSCT.

RESULTSIn 20 MM patients with median age 52.5 (38-66), the neutrophil and platelet counts recovered at 10(8-18) d and 10 (8-17) d after auto-HSCT respectively, the treatment related mortality during 100 days after auto-HSCT was 0, the partial remission (PR) rate decreased from 31.58% to 0 (P < 0.05) after auto-HSCT, only 1 patient was in progression of disease, all patients were alived.

CONCLUSIONFor patients with MM treated with Auto-HSCT, the BUCY regimen is ideal in safety and response, but the long-term effect still should be observed.

Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and Vd were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target AUC0-inf (defined as median AUC0-inf with a once-daily dosage) of 26.18 mg/lxhr, was proposed: 24.79xABW0.5 mg q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.
Body Weight ; Busulfan ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Prospective Studies ; Retrospective Studies

OBJECTIVE: To evaluate the safety and efficacy of BUCY (busulfan and cyclophosphamide) conditioning regimen for autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 72 MM patients received transplantation in the Hematology Department of the First Affiliated Hospital of Soochow University from May 2012 to June 2015 were retrospectively analyzed. Among them, 36 patients received BUCY conditioning regimen while the others received high-dose melphalan (HDM) conditioning regimen. The complication, post-transplantation hematopoietic reconstitution and efficacy between the two groups were compared. RESULTS: There were no significant differences in sex, age, isotype, stage, induction therapy, mobilization method and proportion of conditioning regimen with Bortezomib between the two groups. The median time of neutrophil engraftment for the patients in BUCY and HDM groups was 10 (8-17) and 10 (9-13) d (P=0.046), and the median time of platelet engraftment was 10 (8-18) and 11 (9-47) d (P=0.017), respectively. The transplant related mortality of the patients in both groups was 2.7%. The CR rates of the patients after ASCT (38.9% and 50.0%) were higher than those before ASCT (27.8% and 19.4%) in the two groups. For the patients in BUCY group, the median follow-up time was 45 (0-61) months. Fifteen patients (41.7%) achieved disease progression. While for the patients in HDM group, the median follow-up time was 52(0-75) months. Twenty-two patients (61.1%) achieved disease progression. CONCLUSION The BUCY conditioning regimen is a safe and effective therapy for ASCT in patients with MM. Besides, in terms of safety and efficacy, BUCY regimen is not inferior to HDM regimen. BUCY regimen may replace HDM regimen as a standard conditioning regimen for ASCT in MM.
Busulfan ; Cyclophosphamide ; Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Myeloma/therapy* ; Retrospective Studies

Objective: To evaluate the efficiency and safety of low intensity conditional regimen for children with Fanconi anemia (FA) receiving allogenic hematopoietic stem cells transplantation (allo-HSCT). Methods: Four patients diagnosed as Fanconi anemia were enrolled in this study. One patient received HLA-identical sibling donor hematopoietic stem cell transplantation, two patients underwent unrelated donor matched (UD) HSCT, and one patient received unrelated cord blood transplantation. The conditional regimen consisted of Busulfan with low dose of cyclophosphamide. Results: All 4 cases succeeded in allo-HSCT. The median time for neutrophils engraftment was 11(9-15) day, median time to platelets (PLT) engraftment was 12 (8-28) day. One case occurred with grade I of aGVHD, 1 case with hemorrhagic cystitis. No patient happened with hepatic veno-occlusive disease (VOD). Conclusion: Low intensity of conditional regimen is efficient and safe which should be recommended for FA patients with HSCT.
Busulfan ; Fanconi Anemia ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning

OBJECTIVE: Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan. METHODS: Busulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally. RESULTS: The weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group. CONCLUSION: Genistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.
Animals ; Atrophy ; Busulfan ; Estrogens ; Fertility ; Genistein ; Gonadotropin-Releasing Hormone ; Humans ; Phytoestrogens ; Rats ; Receptors, Estrogen ; Seminiferous Tubules ; Soybeans ; Spermatogenesis ; Testis ; Testosterone