Little is known about late-onset hemorrhagic cystitis (HC) in children, its relationship to BK virus, and treatment with cidofovir (CDV) following hematopoietic stem cell transplantation (HSCT). We prospectively investigated BK virus reactivation in children who underwent HSCT from a matched related donor for thalassemia or sickle cell anemia following busulfan-cyclophosphamide-based conditioning regimens and analyzed risk factors for development of HC and its treatment with CDV. Grade 2-4 HC occurred in 30 patients with a cumulative incidence of 26% (95% confidence interval [CI] = 18%-34%). The cumulative incidences of BK viruria and viremia were 81% (95% CI = 69%-89%) and 28% (95% CI = 18%-40%), respectively. Multivariate analysis revealed that use of antithymocyte globulin (ATG) (hazard ratio [HR] = 10.5; P = .001), peak BK viruria >100,000 copies/mL (HR = 6.2; P = .004), and grade II-IV acute graft-versus-host disease (HR = 5.3; P = .007) were predictive factors for HC. Nineteen patients with HC were given CDV at 1.5 mg/kg/day 3 times a week, or 5 mg/kg/week. The median duration of therapy was 27 days (range, 21-180 days), and a median of 9 doses were given (range, 6-22). All patients had a complete clinical response (CCR), and 69% had a microbiological response at 4 weeks. Eleven patients with BK virus-related HC receiving supportive care also had CCR. The median duration of HC in these patients was similar to that in patients treated with CDV. None of the patients with HC cleared BK viruria when CCR was achieved. We conclude that late-onset HC is more prevalent in children with sustained high BK viruria who are treated with ATG or who develop graft-versus-host disease. Randomized clinical trials are urgently needed to better define the role of CDV in treating BK virus-related HC.

Fetomaternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem cell transplantation from a mismatched mother to thalassemic patient without an human leukocyte antigen-identical donor. Twenty-two patients with thalassemia major were conditioned with 60 mg/kg hydroxyurea and 3 mg/kg azathioprine from day ؊59 to ؊11; 30 mg/m 2 fludarabine from day ؊17 to ؊11; 14 mg/kg busulfan starting on day ؊10; and 200 mg/kg cyclophosphamide, 10 mg/kg thiotepa, and 12.5 mg/kg antithymocyte globulin daily from day ؊5 to ؊2.

Osteonecrosis of the jaws is being increasingly reported in patients with bone metastasis from a variety of solid tumors and disseminated multiple myeloma receiving intravenous bisphosphonates. Agreement exists that these drugs can initiate vascular endothelial cell damage and accelerate disturbances in the microcirculation of the jaws, possibly resulting in thrombosis of nutrient-end arteries. The role of bisphosphonates in cancer patients with previously treated jaws has yet to be elucidated. The signs and symptoms that may occur before the appearance of evident osteonecrosis include changes in the health of periodontal tissues, nonhealing mucosal ulcers, loose teeth and unexplained soft tissue infection. A series of 30 periodontally involved patients showing osteonecrosis of the jaws that appeared following the intravenous use of bisphosphonates is reported. Clinical management of the avascular necrosis of the jaws in patients treated with bisphosphonates presents several problems. An analysis of the international medical literature shows that surgical treatment of the necrotic jaws in patients treated with bisphosphonates has proven to be ineffective in stopping the pathological process. The use of hyperbaric oxygen and antibiotics are not effective, either. The authors have developed a new protocol for the management of these lesions. Compared with other therapeutic choices, this protocol has introduced the use of ozone therapy as therapeutic support.

No abstract