The utility of imatinib in either the pre-or post-transplant period for Ph chromosome-positive (Ph þ ) ALL is uncertain. In addition, there have been recent concerns regarding imatinib and cardiac toxicity. We investigated the outcome of 32 patients with Ph þ ALL who received an allo-hematopoietic cell transplant (HCT) at the University of Minnesota between 1999 and 2006. The median age at HCT was 21.9 years (range: 2.8-55.2). All patients were conditioned with CY and TBI. GVHD prophylaxis was CsA based. Of the 32 patients, 15 received imatinib therapy pre-or post-HCT (imatinib group) and 17 patients received either no imatinib (n ¼ 11) or only after relapse (n ¼ 6) (non-imatinib group). Overall survival, relapse-free survival and relapse at 2 years was 61, 67 and 13% for the imatinib group as compared with 41, 35 and 35% for the non-imatinib group (P ¼ 0.19, 0.12 and 0.20, respectively). Cardiac toxicity and TRM at 2 years were similar between groups. Thus, patients treated with imatinib in either the pre-or post-transplant setting had trends toward improved outcomes and no increase in cardiac toxicity. We suggest that imatinib be included in the peri-transplant management of all patients with Ph þ ALL.

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose 153 Samarium ethylenediaminetetramethylenephosphonate ( 153 Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153 Sm-EDTMP. Gemcitabine was administered 1day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 F 0.4 mCi; range, 0.67-1.8 mCi).All patients received autologous stem cell reinfusion 2 weeks after 153 Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11of 11patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m 2 ) in combination with 153 Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m 2 /d  4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6-to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1year, there have been no durable responses. Thus, although high-dose 153 Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

Background Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for childhood myelodysplastic syndrome (MDS), there is no consensus regarding patient or disease characteristics that predict outcomes. Procedure We reviewed 37 consecutive pediatric MDS patients who received myeloablative HSCT between 1990 and 2010 at a single center. Results Twenty had primary MDS and 17 had secondary MDS. Diagnostic cytogenetics included monosomy 7 (n=21), trisomy 8 (n=7) or normal/other (n=8). According to the modified WHO MDS classification, thirty had refractory cytopenia and 7 had refractory anemia with excess blasts. IPSS scores were: low risk (n=1), intermediate-1 (n=15), and intermediate-2 (n=21). OS and DFS at 10-years in the entire cohort was 53% and 45%. Relapse at 10-years was 26% and 1-year TRM was 25%. In multivariate analysis, factors associated with improved 3-year DFS were not receiving pre-HSCT chemotherapy (RR=0.30, 95% CI 0.10–0.88; p=0.03) and a shorter interval (<140 days) from time of diagnosis to transplant (RR=0.27, 95% CI 0.09–0.80; p=0.02). 3-year DFS in patients who did not receive pre-HSCT chemotherapy and those who had a shorter interval to transplant (n=16) was 80%. Conclusion These results suggest that children with MDS should be referred for allogeneic HSCT soon after diagnosis and that pre-HSCT chemotherapy does not appear to improve outcomes.

Based on this retrospective analysis at a single institution, the use of imatinib either pre- and/or post-transplant does not appear to significantly impact outcomes for children with Ph+ ALL and allogeneic HCT with the best available donor should be encouraged in CR1.

Large registry studies have shown superior disease-free survival (DFS) with matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT) over chemotherapy alone for patients with B-precursor acute lymphoblastic leukemia (ALL) and a late BM relapse. As most of these patients will not have an MSD, the decision to pursue an unrelated allo-HCT in second remission (CR2) or await a future relapse and perform HCT in third remission (CR3) continues to be debated. Between 1990 and 2006, 41 children with relapsed B-precursor ALL received a myeloablative allo-HCT at the University of Minnesota. Graft sources consisted of matched related donor (n ¼ 11), matched unrelated donor (n ¼ 9), and unrelated umbilical cord blood (n ¼ 21). Before allo-HCT, 15 patients had an early relapse (o36 months from diagnosis) and 26 had an initial late relapse (X36 months from diagnosis). In all, 30 patients (73%) were in CR2 and 11 were in CR3 (27%) at time of allo-HCT. Five year OS/DFS were similar for patients with an early or late marrow relapse, but there was inferior DFS among late-relapse patients transplanted in CR3 compared with CR2 (30% vs 75%, P ¼ 0.04). These results suggest that allo-HCT should be pursued in children after a first marrow relapse, rather than waiting for subsequent recurrence. Bone Marrow Transplantation (2011) 46, 950-955;

Infliximab-daclizumab was used to treat acute and chronic liver and gut graft-versus-host disease (GVHD) in two children after standard immunosuppressive therapy failed. Infliximab (10 mg/kg weekly, 4 doses) and daclizumab (1 mg/kg, days 1, 4, 8, 15, and 22) were given over 1 month. In case 1, grade 2 chronic GVHD of the liver developed 1 year after transplantation and failed to improve with tacrolimus, mycophenolate mofetil, and prednisone. In case 2, corticosteroid-unresponsive grade 3 acute liver and gut GVHD developed on day +37. In both patients, GVHD responded to the infliximab-daclizumab regimen without toxicity and immunosuppressive therapy was discontinued.

Since the introduction of imatinib mesylate, the role of allogeneic hematopoietic cell transplantation (allo-HCT) for CML has essentially been reserved for patients with advanced disease or imatinib resistance. In addition, there have been concerns regarding imatinib associated cardiac toxicity. We investigated the outcome of 61 patients with CML who received a myeloablative allo-HCT at the University of Minnesota between 1999 and 2006. The median age at HCT was 38.4 (range; 6.9-56.9) years. Thirty-seven patients were in first chronic phase and twenty-four patients in a second chronic or accelerated phase at the time of HCT. Twenty-six patients received imatinib therapy before or after HCT, and thirty-five patients either never received imatinib (n ¼ 32) or received it only at the time of relapse after HCT (n ¼ 3). OS and relapse-free survival (RFS) at 2 years was 69 and 55% for the imatinib group, and 57 and 49% for the non-imatinib group (P ¼ 0.57 and 0.95, respectively). There was no difference in the risk of relapse at 2 years between the groups. Symptomatic cardiac toxicity at 1 year was reported in three imatinib group (12%) and two nonimatinib group (6%) patients (P ¼ 0.44). Thus, patients treated with imatinib either before or after myeloablative allo-HCT had no increase in cardiac toxicity.

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