stage 3 non hodgkin's lymphoma survival rate | Phomes Malignant non-Hodgkin of the child maximum survival with minimal sequelae

Phomes Malignant non-Hodgkin of the child maximum survival with minimal sequelae



IntroductionLa Survival of children and adolescents with Hodkin disease reaches 90%. 1 In recent decades, the rate of cure for non-Hodgkin malignant lymphoma (NHL) of the child has risen from less than 20% to more than 80%, as long as the disease is detected quickly and the child is immediately assigned to a pediatric oncology unit. Vignette CliniqueUn Eleven-year-old boy, whose history is otherwise uncharacteristic, complains of having a sore back for a week, After a fall. He's been coughing for four days. The last morning he rose as usual. At noon he had no appetite and went to bed. Soon after he starts to have trouble breathing, he stirs, rises and walks in the room raising his arms, then becomes cyanotic and panics. He is then transported urgently to the district hospital where he is immediately intubated and treated with antihistamines and adrenaline, without his condition improving. It is then transferred urgently to the intensive care unit of the nearest university hospital where there is a superior cave syndrome and a jugular vaulted. The additional tests show a large mediastinal mass that even moves the thyroid. Examination of bone marrow is normal but LDH is high at 2378 u/L (norm: L 430 u/L). An open-pit biopsy of the jugular mass is then performed, which shows a relatively well-delimited and well-vascularizeded mass. The extemporaneous examination reveals an undifferentiated small cell tumor suggesting malignant lymphoma, neuroblastoma, or other undifferentiated tumor. Treatment against neuroblastoma was initiated but, very soon, the diagnosis was revised and replaced by a non-Hodgkin's T-cell lymphoblastic lymphoma. The boy develops bradycardia and intracranial hypertension, his neurological condition worsens, he develops a conjugated deviation from the eyes to the right, the pupils no longer react. A mild tomographic examination highlights frontal and parietal hypodenses lesions on both sides. By using all available personal and material resources, the situation can finally be stabilized, Prednisone begins to act. On the tenth day, the child is transferred to the Pediatric Oncology unit. It is then treated according to the protocol NHL-BFM 90: Induction-Protocol M réinduction-maintenance. The boy is recovering well. Two years after the end of treatment he is doing well, growing up normally and can follow in school. Definition NHL is a heterogeneous group of tumors linked to blocked differentiation and a malignant proliferation of B, T or NK lymphocyte precursors. The NHL is distinguished from leukemias by their tissue origin. By definition, in the NHL the bone marrow includes L 25% of tumor cells while beyond that we talk about leukemia. The child's NHL spectrum is more restricted than in adults, but the child's NHL growth is much faster and disseminated to the bone marrow and the early central nervous system. A form of NHL, Burkitt's lymphoma, is associated with Epstein-Barr virus (EBV), especially in tropical Africa (L 90% of cases), less often in Europe or the United States (10-20% of cases). Epidemiology in Switzerland, of 1980-1992, among the 144 children under the age of Fifteen years who developed a cancerous disease each year, 11.5 (8%) had an NHL, 8.5 boys (5.9%) and 3 girls (2.1%), i.e. 2.8 boys for a girl. The decrease in immune defenses, acquired or genetically transmitted, promotes the development of an NHL without being the cause. Etiologyen 1958, Denis Burkitt was the first to describe the NHL that bears his name. The Association of Burkitt lymphoma with malaria and the discovery of Epstein-Barr virus has suggested that it may be the cause of Burkitt's lymphoma. This hThe lymypothèse was abandoned in view of the existence in Europe and the United States of NHL similar to the lymphomas of Burkitt but without association with EBV. Today, it is known that L 90% of Burkitt or Burkitt-like NHL lymphomas are characterized by a 8q24 translocation that causes activation of the C-Myc oncogene. More than a third of the large-cell diffuse B NHL have the same translocation. In adults, 40-60% of the large-cell diffuse B-NHL have a phenotype similar to the cells of germ centres; In children this figure is more than 90%. Symptomatology and DiagnosticLa History of an NHL depends on its initial location (table 1). The child's NHL has such a high rate of growth and, at the same time, such a level of cell destruction, that an emergency hospitalization in a pediatric oncology unit is required as soon as an NHL diagnosis is suspected. Some acute situations related to tumor localization, such as acute asphyxiation due to mediastinal or ent NHL, surgical complication of abdominal lymphoma, compression of excretory pathways, hypercalcemia, insufficiency Renal or urates nephropathy can put the vital prognostic in play and require immediate and well-adapted gestures. It is important to remember that surgical opening of the abdomen is unnecessary, or even dangerous, except in cases of irreducible intestinal intussusception, often caused by a small tumor, easily résecable without sacrifice Important intestinal. There is also a need to avoid general anesthesia in a patient with respiratory distress. The diagnosis is based on histology and immunological, karyological and molecular examinations. Phenotyping is preferably carried out on fresh suspended cells and requires a sufficient number of viable tumor cells (at least 5 million). Phenotyping can also be done by immunoperoxidase on histological sections of fresh frozen tissue, and on unfixed cytological samples, but this examination cannot be done on paraffin cuts, with many surface antigens Then destroyed by this mode of preparation. Karyological and molecular studies also require fresh tumor cells and, for comparisons, also viable normal cells. When a cell sample is carried out on an effusion, or during a biopsy or a spinal puncture, these requirements must always be taken into account in order to be assured of being able to determine the type of NHL correctly. NHL classification of The EnfantD'après the REAL (Revised European American Lymphoma Classification, 1994) and The WHO Classification (2001) are distinguished from the indolent (low grade), aggressive (intermediate grade) and very aggressive (high grade) NHL classifications. Virtually every NHL in the child belongs to the last group (table 2). Lymphomas of BurkittEn Tropical Africa, Burkitt lymphomas represent 95% of the child's NHL and up to 70% of all young cancers. In Africa, EBV is found in L 90% of Burkitt tumours (endemic Burkitt lymphoma, with preferential face damage and/or neurological impairment (paralysis of lower limbs without invasive cerebrospinal fluid)), while in Europe and the United States less than 15% of Burkitt tumours host EBV (non-endemic Burkitt lymphoma with preferential abdominal injury). Endemic Burkitt lymphomas are more susceptible to chemotherapy than non-endemic Burkitt lymphomas. After treatment, possible relapses occur mainly during the first year, so that a child surviving without relapse after a year can be considered cured. Lymphomas LymphoblastiquesLa Majority (75%) of lymphoblastic lymphomas develops in the thymus. When difficulty breathing or swallowing occurs, the disease is already widespreadT has reached the bone marrow, the lymphatic system, the liver, the bones, the skin and often the central nervous system, even the testicles. Therefore, these lymphomas should be treated as T-cell lymphoblastic leukemia. Relapses usually occur during the three years after the initial treatment. Large-cell Diffuse B-cell lymphomas are rare in children; Their incidence increases from the age of fifteen years to reach the figures found in adults. DNA-chip analyses made it possible to distinguish two types with different prognosis: a first cell phenotype of germ centers (GC type) and a second with B cells "activated", a little more differentiated (ABC type). In adults, 40-60% of large-cell diffuse B lymphomas are GC-type, in children this proportion exceeds 90%. The GC type has a better prognosis than the ABC type. This type of lymphoma is expressed preferably in the bone, digestive tract, mediastinum and lymph nodes. After induction of a complete remission, relapses can occur up to five years. Anaplastic lymphomas with large cellulesCes lymphomas are characterized by often inflammatory and painful lymph nodes, associated with fever and single or multiple lesions of the skin in the form of red inflammatory plaques in Tumor ganglia look. Relapses after treatment are rare but can occur up to five years after the initial treatment. Initial assessment and factors PronostiquesBilan general and métaboliqueDès The assumption of a child who is suspicious of an NHL, it is necessary to confirm the Diagnosis, specify the type of lymphoma, and perform a general and metabolic assessment including the following: respiratory, digestive, nutritional, infectious and neurological status, including vision and hearing. CBC, Ionogram, Y including Calcemia and phosphorémie, determination of urea, creatinine and uric acid, hepatic balance, dosage of LDH and measurement of urine output. Initial1 extension balance. Essential Examinations: X-ray of the thorax and cavum. Abdominal ultrasound by a trained specialist. Bone marrow removal on two sectors. Spinal biopsy in the case of NHL B large cell or NHL anaplastic large Cells. Lumbar puncture with cytological study of cerebrospinal fluid. 2. Optional exams, to be performed according to the context: scanner of the head and neck. Abdominal scanner. myelography. Bone Scan. Positron emission tomography (PET-scan). Prognosis factors The most important prognostic factors are: the stage (table 3), the NHL immunophénotype and the value of LDH (children up to one year: L 1000 u/L; Children and adolescents up to fourteen years: L 430 u/l; adults: L 250 u/L). traitementLa Chemotherapy is now the main treatment of the NHL. The surgery still has three main indications: a) the biopsy necessary to diagnose if other sources of cells are not accessible or if the biopsy allows at the same time the complete removal of a very localized tumor Which will later benefit from a light treatment; b) in the presence of an acute abdomen: irreducible intussusception, intestinal perforation, suspicion of appendicitis or severe gastrointestinal hemorrhage and C) for a second look. Radiotherapy is used only exceptionally for irradiation of the central nervous system in the event of initial meningeal impairment, as well as for irradiation of a persistent mass in the mediastinum. The determinants for chemotherapy are on the one hand the Immunophénotype (B or T), and on the other hand the stage. For stage I and II NHL, intensive two-month induction and consolidation with or without neuromeningitis prophylaxis, depending on specific circumstances, resulted in healing rates in the order of 90% pFor Burkitt-type lymphomas and large-cell diffuse B NHL and for large-cell anaplastic NHL. 2to the NHL lymphoblastic stage I and II, induction and consolidation must be followed by a six-month maintenance phase To get similar results. 2to the NHL stage III and IV, a heavier treatment, lasting about eight months for the B-cell NHL, and eighteen to twenty-four months for the immunoblastiques NHL, combined with neuromeningitis prophylaxis Obligatory, produces results comparable to those achieved for the NHL stages I and II. 3-5 from the classical protocols LMB 89 of the French Society for the Cancer of the Child (/verifyonly) to treat the NHL to cells B, 3 and NHL-BFM 90 to treat the NHL Stages III and IV T-cell lymphoblastic of the Gesellschaft für Pädiatri Onkologie und Hämatologie, 5 have appeared treatment modalities to eliminate cranial irradiation and others to explore the potential role of Some naked or conjugated monoclonal antibodies directed against specific antigens of lymphoma cells. 6the B Large cell lymphomas are treated as Burkitt lymphomas with comparable efficacy. Large cell anaplastic lymphomas also respond to short treatments (four to seven months), similar to those used for Burkitt NHL. Relapses are difficult to treat, a sustainable remission is obtained in 10 to 30% of cases Only, generally after ablation by administration of alkylating agents at high doses and transplantation of autologous or allogeneic hematopoietic stem cells. Up to 50% of the CNS-isolated relapses can be controlled by conventional radiation therapy treatments. SéquellesLes sequelae After treatment are sterility due to alkylating agents, heart failure ( anthracyclines), secondary neoplasia and psychic problems. To advise and follow the healed children of an NHL, controls in a specialized centre once a year are recommended. ConclusionUne close cooperation between the pediatrician or the family doctor and the Pediatric oncology specialists is necessary to achieve maximum survival with minimal sequelae. This cooperation is characterised by: transfer of the child or young person to a pediatric oncology unit as soon as possible to confirm the diagnosis, establish an initial assessment of the extent of the lymphoma, begin treatment and To take care of the patient and his family in a holistic way, the psychosocial aspect being here very important. The information of the primary medical practitioner (pediatrician or family doctor) as soon as the diagnosis, the stage and the type of treatment are defined. This includes how the patient and his or her family have been informed about the disease, its treatment and its consequences. The organization's clear definitionmonitoring. Different modalities of shared care are possible, but the pediatrician or family doctor must be included in the patient's follow-up. Thanks to the fact that in Switzerland all children and adolescents with cancer have access to the best treatments available, survival is optimal and the sequelae are minimized. In Switzerland, the success of pediatric oncology is based on the one hand on co-operation between primary practitioners and specialists, on the other hand on the collaboration of specialists in the major international groups devoted to research Clinical. AbréviationsBFM: Berlin Frankfurt MünsterCFR: LeucovorineLNH: Malignant lymphoma non-Hodgkin's local radiotherapy (involved field) Bibliographie1 Wagner HP. The child's Hodgking disease. Maximum survival with minimal sequelae. Rev Med Switzerland 2006; 2:2812-5.2 Link M, Shuster JJ, Donaldson SS, et al. Treatment of children and young adults with early-stage Hodgkin's lymphoma. N Engl J Med 1997; 337:1259-66.3 Paw C, Amperin A, Michx J, et al. The French Society of Pediatric Oncology LMB 89 Protocol: Highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001; 97:3370-9.4 Woessmann W, Seidemann K, Mann G, et al. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: A Report of the BFM Group Study NHL-BFM95. Blood 2005; 105:948-58.5 Reiter A, Schrappe M, Ludwig WD, et al. Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival of children with T-cell lymphoblastic lymphoma: a BFM group report. Blood 2000; 95:416-21.6 Cairo MS. The potential role of monoclonal antibody therapy in The treatment of childhood and adolescent non-Hodgkin lymphoma (NHL). Pediatr Blood Cancer 2004;