Dramatic response to nivolumab in xeroderma pigmentosum skin tumor.

We report the case of a 6-year-old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti-programmed cell death protein 1 (anti-PD-1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation.

Highly sensitive assessment of neuroblastoma minimal residual disease in ovarian tissue using RT-qPCR-A strategy for improving the safety of fertility restoration.

BACKGROUND: Ovarian tissue cryopreservation (OTC) is the only option available to preserve fertility in prepubertal females with neuroblastoma (NB), a childhood solid tumor that can spread to the ovaries, with a risk of reintroducing malignant cells after an ovarian graft. PROCEDURE: We set out to determine whether the analysis of TH (tyrosine hydroxylase), PHOX2B (paired-like homeobox 2b), and DCX (doublecortin) transcripts using quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) could be used to detect NB contamination in ovarian tissue. Analyses were performed on benign ovarian tissue from 20 healthy women between November 2014 and September 2015 at the University Hospital of Clermont-Ferrand. Pericystic benign ovarian tissues were collected and contaminated with increasing numbers of human NB cells (cell lines IMR-32 and SK-N-SH) before detection using RT-qPCR. RESULTS: TH and DCX transcripts were detected in uncontaminated ovarian tissue from all the donors, hampering the detection of small numbers of tumor cells. By contrast, PHOX2B was not detected in any uncontaminated ovarian fragment. PHOX2B levels were significantly increased from 10 NB cells. Our study is the first to evaluate minimal residual disease detection using NB mRNAs in human ovarian tissue. Only PHOX2B was a reliable marker of NB cells contaminating ovarian tissue. CONCLUSIONS: These results are encouraging and offer hope in the near future for grafting ovarian tissue in women who survive cancer, whose fertility has been jeopardized by treatment, and who could benefit from OTC without oncological risk.

Leukapheresis in management of hyperleukocytosis in children's leukemias.

We describe 16 leukapheresis (LK) procedures performed in 7 children with different types of leukemia and hyperleukocytosis. We also provide an analysis of previously published experiences of pediatric LK. Median age and body weight of patients were 12.3 years (range, 0.2 to 16.7 y) and 49 kg (range, 5 to 61 kg). Immediate pre-first-LK median white blood cell count was 478×10/L (108×10/L to 988×10/L). All cytoreduction were performed on Cobe Spectra cell separator. Sixty-eight percent of procedures were performed with peripheral veins. Extracorporeal line had been primed with red blood cell for 31% of LK. The median decrease in white blood cell count after each LK was 33% (0% to 69%), and overall decrease after completion of LK procedures was 62% (11% to 94%). Only minor clinical adverse events and no metabolic complication were attributable to LK. No more clinical symptom of hyperleukocytosis was observed after completion of LK procedures. Our findings are consistent with reported results in other pediatric series: LK is a well-tolerated procedure that can be safely performed with an experienced pediatric team even on the smallest children.

Mobilization of hematopoietic stem cells by plerixafor alone in children: a sequential Bayesian trial.

BACKGROUND: The rapid kinetics of hematopoietic stem cells induced by Plerixafor (Mozobil®, Genzyme) should be of particular interest in children. We therefore conducted a prospective trial to determine whether a one-day mobilization by plerixafor alone was efficient enough in children with cancer. METHODS: Children with solid malignancies were consecutively recruited for this phase-IIA, Bayesian single-center prospective study. Mobilization consisted in one subcutaneous injection of 240 µg plerixafor/kg body weight at 8a.m. (h0). Collection by apheresis began at h5 provided that CD34+count exceeded 10 × 10(6)/L. Our main evaluation criterion was percent of children in which at least 5 × 10(6) CD34+/kg could be collected during the first apheresis. RESULTS: No patients fulfilled the success criterion, and so a stopping criterion was met after 5 patients. All patients reached the threshold value of 10 × 10(6) CD34+cells/L post-injection and so all were eligible for apheresis. Peak CD34+cell values were ranged from 11 to 44 × 10(6)/L and were reached in 4h to 6h. No side-effects were observed. Median number of CD34+cells collected per patient BW was 1.62 × 10(6)[0.47-3.5]. In 3 of the 5 patients, collection was>1.5 × 10(6) CD34+/kg BW. CONCLUSION: In children, a 'one-day' mobilization regimen consisting of one injection of 240 µg/kg plerixafor alone in hematological steady state provides a faster and shorter mobilization than in adults. This strategy may be an attractive option for completing an insufficient graft. More studies are warranted to optimize the use of plerixafor in children.

[Pediatric medical evacuations from Reunion Island to metropolitan France]. / Évacuations sanitaires pédiatriques en oncologie et en hématologie de l'île de la Réunion vers la France métropolitaine.

BACKGROUND: The only French center for pediatric oncology and hematology outside of the metropolitan territory is in the Indian Ocean, in Saint Denis, on Reunion Island. It welcomes children from Reunion Island but also from Mayotte and neighboring countries. A quarter of them requires a secondary medical transfer to metropolitan France for specific technic care. METHOD: We conducted a retrospective single-center study of all pediatric medical evacuations that occurred between 2015 and 2019 from the pediatric oncology and hematology department of Reunion Island. The purpose of this study is to describe these transfers and the consequences of these care pathways for families and care teams. RESULTS: A total of 189 transfers took place for 105 children: 66 from Reunion Island, 17 from Mayotte and 22 were foreigners. In total, 92 % of the children received the medical care for which they were transferred to metropolitan France. Difficulties were reported: family for 26 % of them, social in 11 % of cases and medical in 10 % of medical records. CONCLUSIONS: This organization allows children in the Indian Ocean to benefit from similar care than metropolitan children. Many difficulties arise in connection with family and societal breakdowns caused by these transfers. These differences and difficulties are important to know to better accompany patients, families and caregivers in this stage of their medical pathways.

RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess neuroblastoma minimal residual disease in testicular tissue.

Neuroblastoma (NB) is the most common type of extracranial solid tumor in children with a high prevalence in toddlers. For childhood cancer survivors, preservation of reproductive potential is an important factor for quality of life. The optimization of NB minimal residual disease (MRD) detection in testicular tissue is crucial to evaluate the risk of malignant cell reintroduction. The first step in the present study was to assess the accuracy of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect tyrosine hydroxylase (TH), paired-like homeobox 2b (PHOX2B) and doublecortin (DCX) mRNA expression in frozen/thawed testicular tissues of patients with non-obstructive azoospermia (NOA) contaminated (in vitro model) with an increasing number of IMR-32 and SK-N-SH NB cells. Testicular tissues were frozen by slow or snap freezing. The second step was to determine the expression levels of these markers in testicular samples from 4 pre-pubertal males (2 with stage IV NB and 2 with non-NB malignancy). The yield of extracted RNA was similar in testicular samples frozen by slow or snap freezing. In the in vitro model, TH and DCX transcripts were detected in uncontaminated testicular tissues, whereas PHOX2B mRNA was not detected. There was a strong positive association between the number of NB cells used for contamination and PHOX2B transcript levels. For IMR-32 and SK-N-SH NB cell lines, specificity and sensitivity rates of detection were 100% for PHOX2B following in vitro contamination with 10 tumor cells. In testicular samples from pre-pubertal males with and without NB, PHOX2B mRNA expression was not observed, but high expression levels of TH and DCX mRNA were detected, which were similar to expression detected in the in vitro model. Among the markers used in blood and bone marrow for NB MRD studies, the detection of PHOX2B transcripts by RT-qPCR may provide an accurate assessment of NB cells in testicular tissues from males who require fertility preservation.

Cryopreservation of ovarian tissue in pediatric patients undergoing sterilizing chemotherapy.

Significantly improved survival rates in children and adolescents with cancer have put fertility preservation high on the pediatric oncology agenda. Here we report a retrospective single-center study of 13 years experience of ovarian tissue cryopreservation (OTC) before sterilizing treatment in order to define the safety/benefits of OTC and study clinical/hormonal outcomes in girls. From 2000 to 2013, OTC was performed in 36 girls: eight had non-malignant disease and 28 had malignant disease. Laparoscopy was used to collect a third of each ovary that was frozen by a slow cooling protocol. Indications for OTC were 13 auto-, 19 allo-stem-cell-transplantation and 4 sterilizing chemotherapy. Ovarian tissue harvested by intraumbilical laparoscopy led to no major postoperative complications and did not delay chemotherapy. Histological analysis of ovarian tissue showed an average of 9 primordial follicles/mm(2) [0-83] and no malignant cells were identified. Median post-harvest follow-up was 36 months [1-112]: 26 girls were alive in complete remission and 10 had died. Hormonal results were evaluable for 27 patients (median age 17 yrs [5-26]): 16 patients were in premature ovarian insufficiency. OTC sampling one third of each ovary appears to be an appropriate approach to preserve fertility in children without consequences on subsequent therapeutic program.

Prognostic Value of Vascular Invasion in Pediatric Osteosarcomas.

Metastatic status, histologic response, and quality of surgical resection are prognostic factors for osteosarcomas. Pathology reports sometimes describe peritumoral vascular invasion on surgical specimens after neoadjuvant chemotherapy but their prognostic significance as an independent parameter has never been reported. The aim of this study was to evaluate how the presence of this peritumoral vascular invasion could influence survival. We retrospectively analyzed histology, demographics, and outcomes of pediatric patients treated for osteosarcoma in our institutions between January 2007 and December 2012. A single pathologist analyzed the resection specimens after neoadjuvant chemotherapy. Fifty-one osteosarcomas were diagnosed over a 6-year period; nine had metastatic disease at diagnosis. Surgery was performed after neoadjuvant chemotherapy in all cases. We identified peritumoral vascular invasion in the surgical specimens in 15 cases. Two-year event-free survival (EFS) was 78 % (CI95%[64;93]) for patients without vascular invasion versus 48 % (CI95% [21;75]) in patients with vascular invasion, and 2-year overall survival (OS) was 94 % (CI95%[86;100]) for those without vascular invasion versus 79 % (CI95%[57;100]) for others. Multivariate analysis demonstrated correlation of metastatic status and presence of vascular invasion with survival. The histopathological description of peritumoral vascular invasion in surgical specimens of osteosarcoma after neoadjuvant chemotherapy can be considered a prognostic factor and could indicate modification of the postoperative therapeutic strategy.