The Sickle Cell Unrelated donor Transplant trial (SCURT trial) of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is a phase II study of the toxicity and efficacy of unrelated donor hematopoietic cell transplantation in children with severe sickle cell disease (SCD) using a reduced intensity conditioning regimen. Here we report the results for the cord blood cohort of this trial. Eight children with severe SCD underwent unrelated donor cord blood transplantation (CBT) following alemtuzumab, fludarabine and melphalan. Cyclosporine or tacrolimus and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis. Donor/recipient HLA match status was 6/6 (n=1) or 5/6 (n=7), based on low/intermediate resolution molecular typing at HLA -A, -B, and high resolution typing at -DRB1. Median recipient age was 13.7 years (range 7.4 to 16.2 years), and median weight was 35.0 kg (range 25.2 to 90.2 kg). The median pre-cryopreservation total nucleated cell dose was 6.4 × 107 /kg (range 3.1 to 7.6) and the median post-thaw infused CD34 cell dose was 1.5 × 105 /kg (range 0.2 to 2.3). All patients achieved neutrophil recovery (ANC>500/mm3) by day 33 (median 22 days). Three patients who engrafted had 100% donor cells by day 100, which was sustained and five patients had autologous hematopoietic recovery. Six of eight patients had a platelet recovery to > 50,000/mm3 by day 100. Two patients developed grade II acute GVHD. Of these, one developed extensive chronic GVHD and died of respiratory failure 14 months post-transplant. With a median follow up of 1.8 years (range 1 – 2.6), 7 patients are alive with a 1-year survival of 100% and 3 of 8 are alive without graft failure or disease recurrence. Conclusion Based upon the high incidence of graft rejection after unrelated donor CBT, enrollment onto the cord blood arm of the SCURT trial was suspended. However, since this reduced intensity regimen has demonstrated a favorable safety profile, this trial remains open to enrollment for unrelated marrow donor transplants. Novel approaches aimed at improving engraftment will be needed before unrelated CBT can be widely adopted for transplanting patients with severe SCD.

This open-label, dose-escalation study evaluated the safety and efficacy of singleagent gemtuzumab ozogamicin, a humanized anti-CD33 antibody-targeted chemotherapeutic agent, for pediatric patients with multiple relapsed or primary refractory acute myeloid leukemia (AML). Twenty-nine children 1 to 16 years of age (relapsed disease, 19; refractory disease, 10) received gemtuzumab ozogamicin ranging from 6 to 9 mg/m 2 per dose for 2 doses (separated by 2 weeks) infused over 2 hours. All patients had anticipated myelosuppression. Other toxicities included grade 3/4 hyperbilirubinemia (7%) and elevated hepatic transaminase levels (21%); the incidence of grade 3/4 mucositis (3%) or sepsis (24%) was relatively low. One patient treated at 9 mg/m 2 developed veno-occlusive disease (VOD) of the liver and defined the dose-limiting toxicity. Thirteen patients underwent hematopoietic stem-cell transplantation less than 3.5 months after the last dose of gemtuzumab ozogamicin; 6 (40%) developed VOD. Eight of 29 (28%) patients achieved overall remission. Remissions were comparable in patients with refractory (30%) and relapsed (26%) disease. Mean multidrug resistance-proteinmediated drug efflux was significantly lower in the leukemic blasts of patients achieving remission (P < .005). Gemtuzumab ozogamicin was relatively well tolerated at 6 mg/m 2 for 2 doses and was equally effective in patients with refractory and relapsed disease.

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = −0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

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