Clinical and histological study of permanent alopecia after bone marrow transplantation

Abstract: BACKGROUND: Permanent alopecia after bone marrow transplantation is rare, but more and more cases have been described, typically involving high doses of chemotherapeutic agents used in the conditioning regimen for the transplant. Busulfan, classically described in cases of irreversible alopecia, remains associated in recent cases. The pathogenesis involved in hair loss is not clear and there are few studies available. In addition to chemotherapeutic agents, another factor that has been implicated as a cause is chronic graft-versus-host disease. However, there are no histopathological criteria for defining this diagnosis yet. OBJECTIVE: the study aims to evaluate clinical and histological aspects in cases of permanent alopecia after bone marrow transplantation, identifying features of permanent alopecia induced by myeloablative chemotherapy and alopecia as a manifestation of chronic graft-versus-host disease. METHODS: data were collected from medical records of 7 patients, with description of the clinical features and review of slides and paraffin blocks of biopsies. RESULTS: Two distinct histological patterns were found: one similar to androgenetic alopecia, non-scarring pattern, and other similar to lichen planopilaris, scarring alopecia. CONCLUSION: The first pattern corroborates the literature cases of permanent alopecia induced by chemotherapeutic agents, and the second is compatible with manifestation of chronic graft-versus-host disease on scalp, that has never been described yet. The results contribute to the elucidation of the factors involved in these cases, including the development of therapeutic methods.

Feasibility of Non-TBI Conditioning with Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation in Lymphoid Malignancy

BACKGROUND/AIMS: This retrospective study evaluated the transplantation outcomes of patients with adult lymphoid malignancies who received chemotherapy-based conditioning with busulfan and fludarabine (BuFlu) and busulfan and cyclophosphamide (BuCy2). METHODS: Thirty-eight patients (34 with acute lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for the remaining 24 patients. Eight and 13 patients were high risk disease in the BuCy2 and BuFlu groups, respectively. RESULTS: The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 56.5% and 55.2% and that of extensive chronic GVHD 17.0% and 55.6% (p = 0.018) for the BuFlu and BuCy2 groups, respectively. The 3-year relapse rate was 27.8% and 31.4% and 3-year overall survival 34.3% and 46.8% for the BuFlu and BuCy2 groups, respectively. Treatment-related mortality (TRM) was significantly lower in the BuFlu group (16.9%) than in the BuCy2 group (57.1%, p = 0.010). In multivariate analyses, the BuFlu regimen was identified as an independent favorable risk factor for TRM (hazard ratio [HR], 0.036; p = 0.017) and extensive chronic GVHD (HR, 0.168; p = 0.034). CONCLUSIONS: Our BuFlu regimen would appear to be an acceptable conditioning option for lymphoid malignancies, including high-risk diseases. It was safely administered with a lower TRM rate than BuCy2 conditioning.

[ protective effects of melatonin on the histological changes of testis in busulfan-treated adult mice]

Antineoplastic chemotherapy is usually accompanied by fertility impairment and the aim of this study was to investigate the possible protective effects of melatonin, a pineal gland hormone with potent antioxidant activity, on busulfan-treated adult male mice. This study was performed on 32, eight-week old adult male mice. The animals were divided into four groups consisting of a control and three experimental groups. The animals in the control group received dimethyl sulfoxide [DMSO], a solvent, the second group a single dose of intraperitoneal busulfan [20 mg/kg], the third group a single dose of intraperitoneal melatonin [10 mg/kg] for five days and the fourth group melatonin [10 mg/kg] for five days upon an initial dose of busulfan [20 mg/kg]. Thirty-five days after the treatments, all the animals were sacrificed and dissected. Johnson is score were determined by examining the morphometric characteristics of seminiferous tubules and estimating Leydig cell volumes and germ cell counts. Busulfan-treated mice showed reductions in Johnson's score and quality of spermatogenesis [p<0.001] in comparison to the controls. The quantitative values of seminiferous tubules [p<0.05] and the nuclear volume of Leydig cells [p<0.05] were significantly lower in the busulfan-treated mice relative to the controls. In the fourth group, melatonin not only caused a remarkable normalization in seminiferous tubule indices [p<0.05], but also increased the nuclear volume of Leydig cells [p<0.001], the relevant Johnson's score [p<0.001] and all germ cells in comparison to the second group [p<0.05]. Melatonin might have a possible protective effect against busulfan-induced testicular damage. Although the protective mechanism of melatonin has not been fully revealed, the protection seems to be through a decrease in oxidative stress

[ protective effect of melatonin on sperm parameters, epididymis and seminal vesicle morphology in adult mouse treated with busulfan]

The aim of this study was to investigate the protective effect of melatonin on sperm parameters, epididymis and seminal vesicle morphology in adult mouse under chemotherapy. Male adult NMRI mice were divided into four groups. The control group received a single dose of DMSO, Group 2 received a single dose of busulfan 20 mg/kg. Group 3 was administered melatonin 10 mg/kg for 5 days. Group 4 received a 5 days course of melatonin 10 mg/kg following an initial dose of busulfan 20 mg/kg. Animals were sacrificed 35 days after treatment and evaluations were made by determining of sperm count and sperm quality, histological study of epididymis, seminal vesicle and measuring of plasma testosterone level. Statistical analyses were performed using ANOVA and Tuckey test. Busulfan significantly reduced sperm count, sperm motility and normal morphology and testosterone level in comparison with that of control group [P< 0.01]. However, combined treatment increased mentioned parameters in compare with those of chemotherapy treated group [P< 0.01]. In histological evaluations busulfan resulted in vacuoles in epithelial thickness of epididymis and reduced epithelial cell height in comparison with that of control group [P< 0.001]. Busulfan reduced semen fluid and epithelial folds and epithelial cell height in seminal vesicle in comparison with those of control group [P< 0.001]. However, combined treatment, resulted in recovery and normalization of the epididymis and seminal vesicle. Melatonin has protective effect on epididymal sperm parameters, seminal vesicle and epididymis morphology in mouse under treatment with chemotherapy. Although the mechanism is not clear, it acts probably by decreasing oxidative stresses

[Early hepatic complication in frst year after bone marrow transplantation in major beta thalassemic patients]

Bone marrow transplantation is a good therapeutic modality for beta thalassemia. Liver complications is one of the major causes of morbidity and mortality following BMT. Determination of the factors of liver injury leads to earlier diagnosis after BMT and improves prognosis. We studied 113 major Beta thalassemic patients who have been transplanted from 1990- 2000 in bone marrow transplantation center of Shariati Hospital. 62 were male and 51 were female. 27 patients were class one, 56 were class two and 30 were class three. The median age of each classes were 6.5, 6.3 and 8.7 year. Conditioning regime consisted of busulfan [3.5-4mg/Kg] and cyclophophamide [40-50 mg/kg]. For GVHD prophylaxis we gave cyclosporine +/- metothrexate. Grade of liver fibrosis defined by biopsy in all patients before BMT. All patients and their donors tested for HBsAg, HBsAb, HCVAb, CMVAb with RIA method. We assessed causes of liver dysfunction before and after transplantation and effect of high ferritin level on liver function. Hepatic dysfunction in first year after transplantation were seen in 86 [76%] patients. Causes of liver dysfunction were consisted of 53.1% GVHD, 15.93% cyclosporine hepatotoxicity, 5.3% conditioning regime hepatotoxicity and 1.77% VOD. In all three classes hepatic GVHD, cyclosporine toxicity, death and normal liver function post BMT had significant relation with hepatic dysfunction before BMT [p=0.001]. In patients with ferritin level more than 1000, there were significant hepatotoxicity with conditioning regime [p=0.001]. 17 [15.04%] of patients have been died. In this study we determined incidence and causes of hepatic dysfunction before and after BMT in major beta thalassemic patients. According to our study the incidence of hepatic dysfunction was 76.1% and hepatic GVHD and drug hepotoxicity were the most common causes of hepatic dysfunction in all three classes. Serum ferritin level had not significant relation to GVHD, cyclosporine hepatotoxicity and VOD

Chronic granulocytic leukaemia. A study of 160 cases.

Chronic granulocytic leukaemia (CGL) is the commonest leukaemia among adults in India. Case records of 183 CGL patients diagnosed between 1975 and 1985 were reviewed. The median age at diagnosis was 40.5 years. Most patients presented with weakness, fullness in the left upper abdomen and fever. Splenomegaly and hepatomegaly were present in 90% and 48% respectively. Patients were treated with oral, intermittent busulphan with monitoring of total leucocyte count. Overall, 87 patients expired, including 63 (72%) due to blast crisis. The median survival was 33 months from diagnosis and 44 months from the onset of symptoms.