[Pediatric aphereses (workshop SFGM-TC)]. / Cytaphérèses pédiatriques (atelier SFGM-TC).

Practice of pediatric aphereses - in particular when caring for low-weight children - differs from the practice of adult aphereses, since pediatric aphereses represent low numbers of procedures, which has practical implications in terms of practical training and retraining for involved healthcare personnel, as needed for habilitation and validation of ongoing competencies. A specific training is mandatory in order to ensure both the child and the staff safety during and after collection, as well as ensure high quality of the collected cell product and that its meets predefined specifications that depend on its intended use. Low and very low-weight children deserve a particular attention for a number of procedural and clinical aspects: the nature and quality of venous accesses to ensure proper operation of the cell separator, management of hemodynamic fluctuations in relation with the relative importance of the extracorporeal blood volume as compared to the total blood volume of the child, risks and clinical manifestations of citrate toxicity, minimization of stress during the procedure that may include but is not limited to pharmacological sedation. The full spectrum of competencies needed to deal with these aspects is rarely present within a single team of healthcare professionals; it most often requires the tight combination of expertise drawing from the collection facility, the pediatric department and possibly the pediatric intensive care unit ward, whether from the same or from different institutions. Interactions must be formalized in a document that accurately describes which category of actors is responsible for each category of acts (prescriptions, decisions), depending on their initial qualifications, specific competencies, and affiliations.

Genetic characterization of a unique neuroendocrine transdifferentiation prostate circulating tumor cell-derived eXplant model.

Transformation of castration-resistant prostate cancer (CRPC) into an aggressive neuroendocrine disease (CRPC-NE) represents a major clinical challenge and experimental models are lacking. A CTC-derived eXplant (CDX) and a CDX-derived cell line are established using circulating tumor cells (CTCs) obtained by diagnostic leukapheresis from a CRPC patient resistant to enzalutamide. The CDX and the derived-cell line conserve 16% of primary tumor (PT) and 56% of CTC mutations, as well as 83% of PT copy-number aberrations including clonal TMPRSS2-ERG fusion and NKX3.1 loss. Both harbor an androgen receptor-null neuroendocrine phenotype, TP53, PTEN and RB1 loss. While PTEN and RB1 loss are acquired in CTCs, evolutionary analysis suggest that a PT subclone harboring TP53 loss is the driver of the metastatic event leading to the CDX. This CDX model provides insights on the sequential acquisition of key drivers of neuroendocrine transdifferentiation and offers a unique tool for effective drug screening in CRPC-NE management.

Donor Lymphocyte Infusions After Allogeneic Transplantation: A Single-Center Experience.

Allogeneic hematopoietic cell transplantation (AHCT) represents the only curative therapy for many hematological malignancies. The graft versus leukemia effect, driven by donor T cells, plays a major role in its curative potential. This effect is sometimes very evident when patients with acute myeloid leukemia and myelodysplasia relapse after AHCT and are treated with donor lymphocyte infusions (DLIs). We retrospectively reviewed the charts of 64 patients who received DLI between 2012 and 2017 in our center. The mean age of the patients was 59 years (range, 34-79). Fifty percent were male (n = 32). The mean follow-up time after AHCT was 50.17 months (range, 8-174). The indication for DLI were disease progression, mixed chimerism, minimal residual disease, and other etiologies in 43.8%, 40.7%, 14%, and 1.5% of patients, respectively. The most common diagnosis was acute leukemia, followed by multiple myeloma. Of all patients, 59.4% received a transplant from a related donor, 39% received a transplant from an unrelated donor, and 1.6% received a transplant from a haploidentical donor. Reduced-intensity conditioning AHCT was the most frequent regimen used (53%). DLI was given alone in 79.7% of patients. Prophylactic DLI was given at 30 days after transplantation in patients who received human leukocyte antigen (HLA)-matched related human stem cell transplantation (HSCT) or 45 to 60 days post-transplant in patients receiving haploidentical HSCT or HLA-matched unrelated HSCT. Patients were treated without graft versus host disease (GVHD) prophylaxis. The use of DLI after transplantation remains a feasible procedure with rates of response >60%. Moreover, DLIs are well tolerated with a GVHD rate <10% in our series. We can hypothesize that in our experience the efficacy of this strategy does not rely on the induction of GVHD.

Influence of detection of pretreatment cytogenetic abnormalities on first complete remission and survival in adult acute lymphoblastic leukemia.

OBJECTIVE: Treatment of acute lymphoblastic leukemia (ALL) in adults focuses on the initial assessment of the prognostic relevant cytogenetic features as well as a response-guided therapy based on molecular data. We examined the importance of molecular-cytogenetic abnormalities for complete remission (CR) rates and the overall survival (OS) in adult ALLs. METHODS: Conventional cytogenetics and fluorescence in situ hybridization were performed on bone marrow cells from 33 newly-diagnosed ALL adults. Two karyotype categories [standard- risk group- normal karyotype, hyperdiplody and other structural aberrations, and high-risk group-t(11q23)/MLL, t(9;22)/bcr-abl, t(1;19), t(8;14), C-MYC and complex karyotype] and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. RESULTS: Chromosomal abnormalities were found in 52% of the cases with a high rate of poor-risk translocations - t(9;22), t(8q24), t(11q23), t(1;19). The total CR rate was 67% and the median time for achievement 2.33 months. Male sex, an age below 35 years and the absence of high risk translocations might have contributed to the high CR rates. Female patients, hyperdiplody, low white blood cells (WBC), and random cytogenetic aberrations had the longest OS. OS, 3- and 5-years survival periods were significantly shorter for poor-risk than standard risk group (p=.015, p=.001 and p=.005, respectively). CONCLUSION: This study emphasizes the lack of influence of cytogenetic aberrations on the CR and the time to achieve CR. However, our observations show that these aberrations are an independent prognostic factor in adult ALL - they allow predicting therapy resistance and the OS time after intense treatment.

Significance of molecular-cytogenetic aberrations for the achievement of first remission in de novo acute myeloid leukemia.

OBJECTIVE: The majority of adults diagnosed with acute myeloid leukemia (AML) display acquired cytogenetic aberrations at presentation. In this article, we present the major cytogenetic findings regarding AML and review their clinical significance for achievement of the first complete remission. METHODS: We studied 71 adult patients with de novo AML, without previous myelodysplasia or alkylating therapy. Conventional cytogenetics and FISH were performed on bone marrow cells. The patients with AML were assigned to 12 subgroups according to established data for cytogenetic, molecular and general laboratory results. The selection of the analyzed parameters is consistent with internationally accepted "prognostic factors" in adult AML. RESULTS: Complete remission upon induction therapy was achieved in 40% of cases (in a mean period of 2.3 months from therapy initiation). The patients with t(15;17) PML-RARA and inv(16)/CBFbeta-MYH11ë demonstrated the highest frequency of complete remission. Patients with hypodiploidy, t(9;22)/bcr-abl and complex karyotypes were therapy-resistant or died within the first three months after AML diagnosis. CONCLUSION: Molecular-cytogenetic findings have an important significance for achievement of first complete remission. However, laboratory and biologic features (age, WBC and LDH) and type of AML have a large influence on the disease outcome.