Stephen Rumelhart

Prostaglandin E1 Bladder Instillations to Control Severe Hemorrhagic Cystitis

Severe hemorrhagic cystitis developed in 6 children after marrow transplantation, 3 of whom had a viral etiology. All 6 patients received instillations of prostaglandin E1 directly into the bladder and 5 of the 6 had complete resolution of hematuria. This finding contrasts with our previous experience with severe hemorrhagic cystitis, particularly the type due to a viral infection, persisting in the face of numerous bladder manipulations. We encourage the use of this nontoxic treatment to gain further information regarding its effect on the bladder epithelium. The mechanism of action remains completely unknown.

Complete heart block in association with graft-versus-host disease.

An infant who received haploidentical BM for severe combined immunodeficiency (SCID) developed acute, reversible complete heart block in association with an exacerbation of GVHD. Respiratory distress and myocardial dysfunction were also seen with this and previous GVHD exacerbations. The patient had not received chemotherapy or radiation prior to BMT. The complete heart block resolved after 1 week of intensive immunosuppression. The association of complete heart block with GVHD is important because the heart block is potentially reversible with prompt, aggressive control of the GVHD.

Effect of in vivo lymphocyte-depleting strategies on development of lymphoproliferative disorders in children post allogeneic bone marrow transplantation.

Summary:T cell depletion (TCD) of marrow is a proven method of graft-versus-host disease (GVHD) prophylaxis in allogeneic bone marrow transplantation (BMT). Nonetheless, TCD is associated with an increased risk of developing post transplant lymphoproliferative disorder (PTLD). Between 1986 and 1998, 241 pediatric patients at the University of Iowa underwent BMT using ex vivo TCD of marrow from mismatched related or matched unrelated donors. Additional GVHD prophylaxis included antithymocyte globulin (ATG) or anti lymphocyte globulin (ALG) post transplant (in vivo TCD). A total of 30 cases of PTLD were identified based upon a combination of clinical, histological, and immunological features. Nearly all cases occurred within 3 months post BMT. A statistically significant increase in PTLD incidence was noted for patients treated with ATG vs ALG (33 vs 9%). While grade I–II acute GVHD was more common in patients receiving ATG vs ALG, no difference in grade III–IV GVHD or overall survival was noted between the two groups. Assessment of immune recovery at various times post BMT revealed significantly fewer T cells in the ATG-treated group, suggesting the deleterious effect of ATG may be due to excessive depletion of donor-derived Epstein–Barr virus-specific cytotoxic T cells. Thus, caution should be exercised in the use of anti-T-cell antibody therapy for additional GVHD prophylaxis in the setting of TCD BMT.

BONE MARROW TRANSPLANTATION IMPROVES SURVIVAL FOR ACUTE LYMPHOBLASTIC LEUKEMIA IN RELAPSE : A PRELIMINARY REPORT

Acute lymphoblastic leukemia of childhood is the most common malignant disease in children greater than 1 year of age. Chemotherapy has improved the survival of children with this disorder. More than 95% of children will achieve a remission with chemotherapy. However, 30% of children with acute lymphoblastic leukemia who achieved a remission will have a relapse sometime after successful remission-inducing chemotherapy. Although a second remission can be induced in most of these children, in 10-40% a remission cannot be induced or they relapse shortly thereafter and develop refractory leukemia. We present in this preliminary report the early results of therapy for refractory leukemia with an intensive preparative regimen for bone marrow transplantation including etoposide, cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Transplantation was done in twenty-three patients with refractory leukemia. Projected survival at 917 days after transplantation in these patients is 43.4% +/- 11%. The survival of these patients so far is similar to the survival of children with acute lymphoblastic leukemia transplanted in second remission. All patients treated with this regimen who had transplantation in relapse were free of leukemia 27 days after transplantation. The results of this preliminary report suggest that an intensive preparative regimen can improve the outlook of refractory leukemia and may rescue some patients who otherwise would have died of their disease.

Favorable outcome to glucocorticoid therapy for engraftment syndrome in pediatric autologous hematopoietic cell transplant.

ES remains an important cause of morbidity and mortality in children undergoing auto‐HCT. Glucocorticoid use in ES is an area of debate. We retrospectively analyzed single‐institution experience from September 2000 through December 2012 to evaluate the use of glucocorticoids in auto‐HCT patients. ES was defined by the occurrence of new onset of non‐infectious fever plus diarrhea, rash, or pulmonary infiltrates 24‐h before or within five days after neutrophil engraftment. Sixty‐five pediatric patients (<21 yr) with different solid tumors underwent auto‐HCTs in the study period. Fifteen patients (23%) fulfilled criteria for ES, of which 13 received methylprednisolone (2 mg/kg IV for 3–5 days). Clinical improvement occurred in all patients within 48 h without significant complications. In the non‐ES group, 11 patients received glucocorticoid without significant complications as well. MEL‐based regimens were found to be significant factor for ES (p < 0.05). Fever, edema, non‐infectious diarrhea, and serum albumin concentration were statistically different between the two groups. Median hospital length of stay was higher in the ES group. Conclusion: ES is a common complication in children after auto‐HCT and short‐course glucocorticoid therapy is an effective and well‐tolerated treatment, even in those who did not completely fulfill diagnostic criteria.