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1.  A comparison of immune reconstitution and graft-versus-host disease following myeloablative conditioning (MAC) vs. reduced toxicity conditioning (RTC) and umbilical cord blood transplantation (UCBT) in paediatric recipients 
British journal of haematology  2011;155(2):218-234.
Immune reconstitution appears to be delayed following myeloablative conditioning (MAC) and umbilical cord blood transplantation (UCBT) in paediatric recipients. Although reduced toxicity conditioning (RTC) vs. MAC prior to allogeneic stem cell transplantation is associated with decreased transplant-related mortality, the effects of RTC vs. MAC prior to UCBT on immune reconstitution and risk of graft-versus-host disease (GVHD) are unknown. In 88 consecutive paediatric recipients of UCBT, we assessed immune cell recovery and immunoglobulin reconstitution at days +100, 180 and 365 and analysed risk factors associated with acute and chronic GVHD. Immune cell subset recovery, immunoglobulin reconstitution, and the incidence of opportunistic infections did not differ significantly between MAC vs. RTC groups. In a Cox model, MAC vs. RTC recipients had significantly higher risk of grade II-IV acute GVHD (Hazard Ratio [HR] 6.1, p=0.002) as did recipients of 4/6 vs. 5-6/6 HLA-matched UCBT (HR 3.1, p=0.03), who also had significantly increased risk of chronic GVHD (HR 18.5, p=0.04). In multivariate analyses, MAC vs. RTC was furthermore associated with significantly increased transplant-related (Odds Ratio 26.8, p=0.008) and overall mortality (HR=4.1, p=0.0001). The use of adoptive cellular immunotherapy to accelerate immune reconstitution and prevent and treat opportunistic infections and malignant relapse following UCBT warrants further investigation.
PMCID: PMC3188698  PMID: 21848882
cord blood transplantation; GVHD; paediatrics; immune; immunology
2.  High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma† 
Neuro-Oncology  2010;12(3):297-303.
Recurrent medulloblastoma is highly lethal in previously irradiated patients. Previously irradiated patients with M-0–M-3 recurrences who achieved a minimal disease state prior to protocol enrollment received carboplatin (Calvert formula with area under the curve = 7 mg/mL min, maximum 500 mg/m2/day) on days −8 to −6, and thiotepa (300 mg/m2/day) and etoposide (250 mg/m2/day) on days −5 to −3, followed by autologous stem cell rescue (ASCR) on day 0. Twenty-five patients, aged 7.6–44.7 years (median 13.8 years) at ASCR, were treated. Three (12%) died of treatment-related toxicities within 30 days of ASCR, due to multiorgan system failure (n = 2) and aspergillus infection with veno-occlusive disease (n = 1). Tumor recurred in 16 at a median of 8.5 months (range 2.3–58.5 months). Six are event-free survivors at a median of 151.2 months post-ASCR (range 127.2–201.6 months). The Kaplan–Meier estimate of median overall survival is 26.8 months (95% CI: 11.9–51.1 months) and of event-free survival (EFS) and overall survival are both 24% (95% CI: 9.8%–41.7%) at 10 years post-ASCR. M-0 (vs M-1 + ) recurrence prior to protocol, lack of tissue confirmation of relapse, and initial therapy of radiation therapy (RT) alone (vs RT + chemotherapy) were not significantly associated with better EFS (P = .33, .34, and .27, respectively). Trends toward better EFS were noted in patients (n = 5) who received additional RT as part of their retrieval therapy (P = .07) and whose recurrent disease was demonstrated to be sensitive to reinduction chemotherapy (P = .09). This retrieval strategy provides long-term EFS for some patients with previously irradiated recurrent medulloblastoma. The use of additional RT may be associated with better outcome.
PMCID: PMC2940591  PMID: 20167818
chemotherapy; hematopoietic stem cell transplantation; medulloblastoma

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