[Non invasive ventilation and pediatric palliative care. A French survey]. / Ventilation non invasive et soins palliatifs en pédiatrie. État des lieux en France.

OBJECTIVES: The benefits of non-invasive ventilation (NIV) have been clearly demonstrated in pediatrics. In palliative care, NIV can improve the level of comfort and quality of life and can decrease dyspnea. The objective was to survey pediatricians' opinions and practices regarding NIV in palliative care in France. DESIGN: A mail survey was conducted among pediatric pneumologists, intensivists and palliative medicine consultants from February 2015 to March 2015. RESULTS: In case of acute respiratory failure, 84% of the responding practitioners found NIV appropriate in do-not-intubate (DNI) children, while only 35% of them found it appropriate in comfort-measures-only (CMO) children (P<0.0001). In case of progressive respiratory failure, 68% of the responders found NIV appropriate in DNI children, while only 30% in CMO children (P<0.05). The major criterion for initiating NIV in pediatric palliative care was the presence of dyspnea. In pediatric palliative care, the efficacy of NIV was evaluated primarily clinically in terms of the improvement of the child's comfort level, as well as the child's and family's satisfaction. Hypercapnia and desaturation were rarely measured to initiate NIV or to assess its efficacy. Sixty percent of the responding practitioners indicated that referral to NIV was anticipated with children and family before acute events or end-of-life occurred. CONCLUSION: French pediatricians habitually use NIV for management of acute or progressive respiratory symptoms in DNI children. In CMO children, a majority of responding practitioners find NIV inappropriate. In palliative care, the indications for and efficacy of NIV are evaluated based on clinical criteria and rarely on gasometric criteria.

High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group.

The optimum treatment of primary CNS lymphoma (PCNSL) is not yet determined. The objective of this study was to assess the safety and efficacy of initial methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) in patients with newly diagnosed PCNSL. Twenty-five patients received two courses of initial chemotherapy combining methotrexate, etoposide, carmustine and methylprednisolone, and one course of ifosfamide-cytarabine followed by peripheral stem cell collection. Seventeen responsive patients then received HDT using carmustine, etoposide, cytarabine and melphalan with autologous stem cell rescue. After ASCT for responding patients or after salvage therapy for non-responders, whole brain radiation therapy at a dose of 30 Gy was delivered. The objective response rate to the induction chemotherapy was 84%. Four of the 21 responding patients did not have ASCT because of toxicity or refusal. With a median follow-up time of 34 months, the projected event free survival rate is 46% at 4 years. Projected overall survival is 64% at 4 years. Sixteen patients are actually in continuous complete response. No evidence of late treatment-related toxicity was observed. This treatment approach appears feasible in newly diagnosed PCNSL with encouraging results.

rHuEpo before high-dose therapy allows autologous peripheral stem-cell transplantation without red blood cell transfusion: a pilot study.

To decrease red blood cell (RBC) transfusion requirements during high-dose therapy (HDT) for hematological malignancies, we conducted a pilot study to assess the effect of recombinant human erythropoietin (rHuEpo) given during chemotherapy before HDT and autologous peripheral stem-cell transplantation (APSCT). The transfusion histories of 15 HDT and APSCT for hematological disease performed in 11 consecutive patients who received rHuEpo (10 000 U subcutaneously three times/week) were compared to those of 22 HDT and ASCT performed in 17 consecutive historical controls matched for hematological parameters. rHuEpo increased the hemoglobin (Hb) level from 10.3+/-2.3 g/dl at diagnosis to 12.9+/-2.2 g/dl at the time of HDT in 11 patients; no major adverse effects occurred. Compared to historical controls (95%, 21/22), RBC transfusion requirements were significantly lower for rHuEpo recipients (26%, 4/15) (P=0.00001) and rHuEpo responders (15%, 2/13) (P=0.000002). After HDT and APSCT, fewer RBC transfusions were needed: 3.3, 1.2 and 0.3 RBC units for controls, rHuEpo recipients and rHuEpo responders, respectively (P=0.006 and 0.00002). Therefore, rHuEpo should be administered before, and not after HDT and APSCT, to lower RBC transfusion requirements after HDT and APSCT.

Increased apoptosis in mononucleated cells but not in CD34+ cells in blastic forms of myelodysplastic syndromes.

INTRODUCTION: Myelodysplastic syndromes are characterized by peripheral refractory cytopenias together with normo or hyper cellular marrow. Increased apoptosis has been shown to be involved in the process leading to this paradox. MATERIALS AND METHODS: Early apoptosis detection, based on the modification of mitochondrial transmembrane potential (deltapsim), was performed on bone marrow cells from 42 MDS patients (21 RA, four RARS, 10 RAEB, two RAEB-t, three sAML, and two CMML) and seven normal healthy donors. Phosphatidylserine (PS) expression, a late/intermediate marker of the apoptotic cascade, was also quantified. Apoptosis was analysed by flow cytometry both on unsorted mononuclear cells and on progenitor cells after CD34+ magnetic cell sorting. RESULTS: A significant increase of apoptosis of MNC was observed in RA, RARS, RAEB and to a lower extent in RAEB-t and AML samples. In the progenitor compartment, RA and RARS samples presented a high level of apoptosis, whereas a switch to a low level of apoptosis was detected in the blastic forms RAEB, RAEB-t and sAML. Fas (CD95/APO-1), a member of the death domain receptor family, has been reported to be overexpressed on MDS CD34+ marrow cells. A functional assay of Fas cross-linking using the CH11 antibody on CD34+ marrow cells was performed on samples of 17 MDS patients; 8/17 were found to be sensitive to Fas-induced apoptosis. However, no correlation was observed with the level of in vivo spontaneous apoptosis. CONCLUSION: This study demonstrates increased apoptosis of MNC in all MDS subgroups as measured by deltapsim collapse. Moreover, while important apoptosis is still observed at the progenitor level in early MDS, blastic forms show a clear reduction of apoptosis. Study of Fas functionality modulates the implication of this receptor in the pathophysiology of the disease.

[Acquired von Willebrand disease and lymphoproliferative syndromes]. / Maladie de Willebrand acquise et syndromes lymphoprolifératifs.

OBJECTIVE: Acquired von Willebrand disease occurs in patients with or without cutaneous and mucosal bleeding who have no personal or family history of the disease. The clinical course of these patients is poorly known due to the rarity of acquired von Willebrand factor (vWF) deficit. We conducted this study to assess the clinical course of acquired vWF deficit secondary to lymphoproliferative syndromes. PATIENTS AND METHODS: We report the clinical course of acquired von Willebrand disease in 6 patients with monoclonal gammapathy of undetermined significance, multiple myeloma, chronic lymphoid leukemia, Wadenstöm's macroglobulinemia, or lymphoma who were followed for 1 to 11 years. RESULTS: Acquired von Willebrand disease was suspected in non-thrombocytopenic patients with a lymphoproliferative syndrome who developed a hemorrhagic syndrome. The vWF anomaly was symptomatic in 4 of 6 patients at diagnosis. Patients were given symptomatic treatment with vWF replacement therapy as needed and specific treatment for their lymphoproliferative syndrome. Administration of DDAVP was sufficient in 3 out of 4 patients to allow invasive procedures but was unable to control digestive ulcer bleeding that required infusion of factor VIII-vWF concentrate. For 2 patients, chemotherapy was initiated due to threatening massive hemorrhage. The result was spectacular. The 4 other patients have been asymptomatic without treatment for 3, 5, 6 and 11 years during which time their lymphoproliferative syndrome has been quiescent. CONCLUSION: The clinical features and laboratory findings are similar in patients with congenital or acquired von Willebrand disease, but specific and etiologic chemotherapy is indicated for patients with acquired disease.

[Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence]. / Localisation sous-rétinienne inaugurale d'une rechute de leucémie aiguë myéloblastique (LAM5).

BACKGROUND: Reduced visual acuity in patients with acute leucemia can result from many causes including an ocular localization. CASE REPORT: A patient previously treated for acute myeloblastic leucemia-5 (AML5) developed bilateral vision impairment related to a subretinal localization of the leucemia. Meningeal and bone marrow relapse followed. The subretinal localization responded only to massive systemic steroid treatment. DISCUSSION: Although asymptomatic, ocular localizations are frequent in leucemia. Their prognostic impact depends on the ocular structure involved and on the chronology of onset--early or late in the leucemia course. The underlying pathophysiological mechanism of ocular involvement remains unexplained but hyperleucocytosis at presentation may be a risk factor and would justify at least systematic specialized examinations and discussion of prophylactic treatment.

[Management of neuropathic pain in children: guidelines for good clinical practice]. / Prise en charge des douleurs neuropathiques chez l'enfant: recommandations de bonne pratique clinique.

Neuropathic pain exists in children and its incidence is often underestimated due to the lack of knowledge on the existence and the diagnosis of this pain. Although the semiological characteristics can be compared to those of the adult (allodynia, hypoesthesia, burning and stabbing sensations), their etiology often differs, and pain treatments are more limited because of a lack of pharmacological data and the absence of clinical studies. Therapeutic management is sometimes insufficient and requires better knowledge of this entity. Based on the June 2009 recommendations of the French Agency for Food and Drug Safety (Afssaps) (drug therapy in acute and chronic pain in children), this article presents a review of the data available in the literature on the subject, taking into account expert opinion and proposing clinical recommendations of good practice for the recognition and the treatment of neuropathic pain in children.

Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies.

BACKGROUND: This randomized study compared the efficacy and safety of fludarabine-mitoxantrone (FM) with mini-CHVP (cyclophosphamide, doxorubicin, vindesine, prednisone) in elderly patients with advanced, low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: End points were remission rates [overall response (OR) and complete response (CR)], failure-free survival (FFS), survival and toxicity. One hundred and fifty-five patients were randomized, 144 were evaluable for safety and 142 for response. Each treatment arm was given as six monthly cycles, followed by three bimonthly cycles. FM comprised fludarabine (20 mg/m(2) i.v.), days 1-5, plus mitoxantrone (10 mg/m(2) i.v.), day 1. CHVP cycles comprised cyclophosphamide (750 mg/m(2) i.v. infusion), doxorubicin (25 mg/m(2) i.v.) and vindesine (3 mg/m(2) i.v.) on day 1, and prednisone (50 mg/m(2)) on days 1-5. RESULTS: FM therapy resulted in superior remission rates (OR 81% versus 64%, CR 49% versus 17%; P = 0.0004). Median FFS for FM patients was 36 months, compared with 19 months for CHVP patients, and has not yet been reached for early CR patients at 53 months. Treatment arm was the major risk factor influencing survival. Both treatments were well tolerated, with only few infectious complications. CONCLUSION: FM was more effective than CHVP in achieving OR and CR, and favorably affected the outcome.