Bone marrow transplantation in pediatric patients with therapy-related myelodysplasia and leukemia.
Eleven children underwent BMT for therapy-related MDS or leukemia, four from HLA-identical siblings and seven from unrelated donors. Ten of the 11 were conditioned with busulfan and cyclophosphamide as the majority had received prior irradiation to the chest and/or abdomen. All patients engrafted. Regimen-related toxicity was more common when compared to historical controls. Eight patients developed acute GVHD and four of eight who survived 100 days post transplant developed extensive chronic GVHD. Non-relapse related mortality occurred in three patients. Five patients developed recurrent malignancy: one died from recurrence of osteosarcoma, three died of recurrent leukemia or MDS and another developed two subsequent malignancies (duodenal carcinoma and anaplastic astrocytoma). Three survive disease-free at 14+, 22+ and 43+ months for a 2 year actuarial cancer-free survival of 24% (95% confidence interval = 5-53%). Although allogeneic BMT can be curative, regimen-related toxicity is frequent and recurrent malignancy remains the major obstacle. (+info)
Risk factors for severe hemorrhagic cystitis following BMT.
Hemorrhagic cystitis (HC) is a common toxicity of preparative regimens for bone marrow transplantation (BMT). Severe HC often requires prolonged and expensive hospitalization, and occasionally can result in death. To investigate the risk factors for severe HC, we conducted a retrospective study among 1908 patients who received BMTs at the University of Minnesota during 1974 to 1993. A previous report from our institution reported on 977 of these patients. We identified all patients with genitourinary complication within 100 days post-BMT from the BMT database. Medical charts for these patients were reviewed to determine whether the patient had HC and also the grade of HC. A total of 208 HC cases were identified during the study period. Of them, 92 patients had severe HC, an incidence of 5% (95% CI = 4-6%). We found that grade II-IV graft-versus-host disease (RR = 2.56; 95% CI = 1.43-4.56), use of busulfan (RR = 2.69; 95% CI = 1.35-5.35), and age at transplant (RR = 2.20; 95% CI = 1.27-3.81, for age of 10-30 compared to age of 0-9) were related to an increased risk of HC. In contrast, transplant year was inversely associated with the risk of HC (trend test, P < 0.01). We did not find any significant difference in HC with the use of prophylactic Mesna. (+info)
Central venous catheter exchange by guidewire for treatment of catheter-related bacteraemia in patients undergoing BMT or intensive chemotherapy.
Current guidelines for the treatment of catheter-related bacteraemia (CRB) advise against central venous catheter (CVC) exchange because of the potential risk of prolonging infection. However, there are no consistent data proving this recommendation. We evaluated prospectively the usefulness of CVC exchange by guidewire for the treatment of CRB in patients undergoing BMT or intensive chemotherapy. CVC exchange was considered when fever and positive blood cultures persisted after 2 days of adequate antimicrobial therapy and no potential source of bacteraemia other than CVC could be identified. The guidewire exchange was preceded and followed by a slow infusion of adequate antimicrobial therapy. Bacteraemia was confirmed as catheter-related by demonstrating concordance between isolates from the tip and blood cultures by pulsed-field electrophoresis of genomic DNA. This procedure was performed in 19 episodes of bacteraemia during a 1-year period. Fourteen episodes (74%) were catheter-related and 71% of these were due to coagulase-negative staphylococci. Guidewire replacement was accomplished uneventfully 4 days after development of sepsis (range 3-6). In all cases, clinical signs of sepsis disappeared in less than 24 h after replacement. Definitive catheter withdrawal was carried out a median of 16 days (range 3-42) after guidewire exchange; in all cases, the tip culture was negative. We conclude that CVC replacement by guidewire under adequate antimicrobial therapy may be a reasonable option for the treatment of CRB when antimicrobial therapy alone has been unsuccessful. (+info)
The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.
At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy. (+info)
Disappearance of lupus anticoagulant after allogeneic bone marrow transplantation.
Lupus anticoagulant antibodies have never been reported to disappear after either allogeneic or autologous bone marrow transplantation in humans. We report the first case of disappearance of lupus anticoagulant antibodies in a patient without systemic lupus erythematosus or clinical evidence of other autoimmune disorders, who received an allogeneic bone marrow transplant as treatment for chronic myeloid leukemia. Although marrow transplantation is not a recognized therapy for antiphospholipid syndrome, our observation should be considered another example of the capability of intensive chemo-radiotherapy followed by stem cell transplantation to ablate a pathologic marrow clone resulting in an autoimmune disorder and improve, or even cure, some severe autoimmune diseases. (+info)
Rapid autologous marrow recovery and eradication of infectious mononucleosis despite severe immunosuppression following second transplantation for aplastic anemia.
A patient with aplastic anemia failed to respond to immunosuppressive therapy and first marrow transplantation (BMT). Recovery of autologous hematopoiesis was rapid following a second stem cell transplant with a non-myeloablative preparatory regimen. The autologous immune response to infectious mononucleosis (IM) 4 weeks post-transplant was normal despite recent and ongoing severe immunosuppression. (+info)
Nephrotic syndrome as a clinical manifestation of graft-versus-host disease (GVHD) in a marrow transplant recipient after cyclosporine withdrawal.
GVHD is one of the most frequent complications of BMT and recently nephrotic syndrome (NS) has been described as a manifestation of chronic GVHD. Here, we present an AA patient who developed NS 1 year after BMT when cyclosporine was stopped. Renal biopsy showed focal sclerosis associated with membranous deposits. He also had other clinical manifestations of chronic GVHD: sicca-like syndrome and colestasis. After 15 days of CsA therapy, he experienced a remarkable improvement in the NS and GVHD as a whole. We comment on immunological mechanisms that could be involved in the pathogenesis of this manifestation. (+info)
Gonadotropin-releasing hormone analogue conjugates with strong selective antitumor activity.
Conjugation of gonadotropin-releasing hormone (GnRH) analogues GnRH-III, MI-1544, and MI-1892 through lysyl side chains and a tetrapeptide spacer, Gly-Phe-Leu-Gly (X) to a copolymer, poly(N-vinylpyrrolidone-co-maleic acid) (P) caused increased antiproliferative activity toward MCF-7 and MDA-MB-231 breast, PC3 and LNCaP prostate, and Ishikawa endometrial cancer cell lines in culture and against tumor development by xenografts of the breast cancer cells in immunodeficient mice. MCF-7 cells treated with P-X-1544 and P-X-1892 displayed characteristic signs of apoptosis, including vacuoles in the cytoplasm, rounding up, apoptotic bodies, bleb formation, and DNA fragmentation. Conjugates, but not free peptides, inhibited cdc25 phosphatase and caused accumulation of Ishikawa and PC3 cells in the G2/M phase of the cell cycle after 24 h at lower doses and in the G1 and G2 phases after 48 h. Since P-X-peptides appear to be internalized, the increased cytotoxicity of the conjugates is attributed to protection of peptides from proteolysis, enhanced interaction of the peptides with the GnRH receptors, and/or internalization of P-X-peptide receptor complexes so that P can exert toxic effects inside, possibly by inhibiting enzymes involved in the cell cycle. The additional specificity of P-X-peptides compared with free peptides for direct antiproliferative effects on the cancer cells but not for interactions in the pituitary indicates the therapeutic potential of the conjugates. (+info)