Fertility impairment and recovery after haematopoietic stem cell transplantation (HSCT) have been reported in both sexes, but little is known about how they develop over time. Our aim was to describe the dynamics of fertility impairment and recovery after HSCT.

Meeting abstracts T-cell receptor (TCR) diversity is characterised by somatic alterations in the complementary determining region 3 (CDR3) of the human TCR β-chain. Complemented with the TCR alpha-chain, TCR diversity can hypothetically result in up to 1018 different TCR molecules. Myeloid

BACKGROUND:For children with hemato-oncologic diseases, especially after hematopoietic stem cell transplantation (HSCT), the risk for developing complications related to pandemic influenza A (H1N1) 2009 (pH1N1) infection is largely unknown.METHODS:A retrospective chart study was performed of pH1N1 cases diagnosed between October 2009 to January 2010 in the hemato-oncologic unit of the University Children's Hospital of Düsseldorf, Germany.FINDINGS:In total, 21 children were diagnosed with laboratory-confirmed pH1N1; in 16 patients with malignancies (acute leukemia 7, lymphoma 4, solid tumors 2, others 3) and in 5 with benign hematologic disorders. Five patients had undergone prior HSCT, although 1 patient was diagnosed during conditioning therapy with high-dose chemotherapy in preparation for haploidentical HSCT. Most frequent symptoms were fever (>38.5°C) and cough (in 100%), and rhinorrhea (57%). The 2 patients acquiring pH1N1 infection under high-dose or intensive chemotherapy did not require intensive care or mechanical ventilation, and both recovered under antiviral therapy. Oseltamivir was administered to 11 patients; in 1 patient, therapy was switched, on a compassionate-use basis, to intravenous zanamivir because of lack of clinical improvement after oseltamivir therapy. Complications were hospitalization (19%), demand of oxygen supplementation, delay/interruption of antineoplastic therapy, and prolonged administration of antibiotics and antipyretics.CONCLUSION:In the investigated patient population, pH1N1 was mild in most cases, but was associated with substantial morbidity in a proportion of patients and led to interruption and delay in anticancer treatment.

Based on the results from the AML-BFM 98 trial, hematopoietic SCT (HSCT) is recommended for children with AML in second CR only. Here, we retrospectively analyze interphase data of children who underwent HSCT after myeloablative conditioning with BU, CY, and melphalan (BuCyMel) for AML in second remission (CR2) between 1998 and 2009. Out of 152 children, transplant data were available on 109 individuals. Sixty out of 109 children (55%) received BuCyMel. Median age at HSCT was 12.2 years (range 3.0; 18.3). GVHD prophylaxis mostly consisted of CsA and short term MTX with or without antithymocyte globulin. Matched-sibling donors were used for 6/60 analyzed recipients, the remainder either received grafts from matched unrelated (30/60) or mismatched donors. OS after 5 years was 62% (s.e. 6%), relapse incidence 35% (18/60 children) and treatment-related mortality accounted for 12% (7/60) of fatal events. In conclusion, even taking into account possible selection bias in this retrospective analysis, HSCT in CR2 using BuCyMel resulted in a respectable OS. Based on this data the prospective, controlled and centrally monitored AML SCT-BFM 2007 trial has started to recruit patients in January 2010 aiming to generate valid outcome data for further strategy decisions.

Chen C, Akanay‐Diesel S, Schuster FR, Klee D, Schmidt KG, Donner BC. An unusual manifestation of post‐transplant lymphoproliferative disorder in the lip after pediatric heart transplantation. Pediatr Transplantation 2012. © 2012 John Wiley & Sons A/S. Abstract: PTLD is a serious and frequently observed complication after solid organ transplantation. We present a six‐yr‐old girl with a rapidly growing, solid tumor of the lip four yr after orthotopic heart transplantation, which was classified as monomorphic PTLD with the characteristics of a diffuse large B‐cell lymphoma. Treatment with reduction in immunosuppression, ganciclovir, and anti B‐cell monoclonal antibody (rituximab) resulted in full remission since 12 months. To the best of our knowledge, this report is the first description of PTLD in the lip in a pediatric patient after heart transplantation in the English literature.

A teenager who acquired 2009 H1N1 influenza A lower respiratory tract infection during total bone marrow and lymphoid aplasia, in the setting of human leukocyte antigen-haploidentical hematopoietic stem cell transplantation, was successfully treated with intravenous zanamivir. This case demonstrates efficient control of pandemic influenza infection by intravenous zanamivir in the absence of any functional immune system, thus suggesting profound antiviral activity.

One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA ( n =10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response ( n =6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity ( n =4, CD8+ complexity scoring median 109.5, range 82–124) always failed ( P =0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation.

Infertility is a major late effect in patients receiving haematopoietic stem cell transplantation (HSCT). The aim of this study was to determine the proportion of patients having fertility impairment after allogeneic HSCT in childhood/adolescence and to identify the potential risk factors. Treatment and fertility data of paediatric patients with malignant and non-malignant diseases treated with allogeneic HSCT between 2000 and 2005 were collected from seven European centres. Data were obtained for 138 female and 206 male patients after a median follow-up of 6 years (range 3–12). The patients’ median age was 13 years (range 4–28) at the time of HSCT and 19 (range 12–35) years at the time of the enquiry. Seven children were born to the overall group, all at term and healthy. Fertility impairment was suspected in 69% males and 83% females. Start of treatment at age ⩾13 years was a risk factor in females (odds ratio (OR) 4.7; 95% confidence interval (CI), 1.5 to 14.9), whereas pre-pubertal therapy was a risk factor in males (OR 0.4; 95% CI, 0.2 to 0.8). The major treatment-related risk factors were BU in females (OR 47.4; 95% CI, 5.4 to 418.1) and TBI in males (OR 7.7; 95% CI, 2.3 to 25.4). In light of the significant proportion of HSCT patients reviewed with impaired fertility, fertility conservation procedures should be considered for all patients undergoing HSCT, particularly those receiving TBI or BU-based preparative regimens.

SUMMARY: Subacute MTX-induced encephalopathy is characterized by an abrupt onset of focal neurologic deficits within days after intrathecal or systemic therapy. Demyelination is one proposed mechanism. We describe the neuroimaging features of 2 patients with clinical symptoms of subacute encephalopathy after intrathecal and systemic MTX therapy. DWI showed restricted diffusion, indicating cytotoxic edema. MTI yielded no evidence of demyelination in either patient because there was no loss of MTR in areas of restricted diffusion.

The morbidity and mortality rates of invasive fungal infection in allogeneic stem cell recipients are still unacceptably high and have not been significantly improved by alternative antifungal strategies to date. Over the last few years, rapid methods for the clinical-scale generation of functionally active and well characterized antifungal TH1 cells have become available. In addition, current data on the use of donor-derived virus-specific T cells in allogeneic stem cell transplantation suggest that the risk of severe adverse events, in particular the risk of graft-versus-host disease, is negligible. Therefore, adoptive antifungal immunotherapeutic strategies should be evaluated in clinical trials. However, one has to recognize that these trials are only meaningful with sufficiently large and homogenous cohorts of patients and if the settings of adoptive antifungal immunotherapy are comparable. Ultimately, the strategy of adoptively transferring antifungal immune responses might improve the outcome in hematopoietic stem cell recipients suffering from invasive fungal infection.