mercaptopurine and Growth-Disorders

Guidelines for treatment of ulcerative colitis in children have been created by the working group of the Japanese Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Japanese Society for Pediatric Inflammatory Bowel Disease. The ideas of these guidelines, with regard to the fundamental differences in medical treatment between children and adults, included (1) for children, intensive medical treatment including appropriate systemic management is important during the acute phase of illness. (2) Treatment with steroids, which can cause growth disturbances, should not be continued for long period of time. (3) Pulsed steroid therapy, selective removal of blood cells, and intravenous infusion of cyclosporin are included in the therapeutic option for severe and fluminant cases.

Topics: Azathioprine; Child; Colitis, Ulcerative; Contraindications; Cyclosporins; Growth Disorders; Humans; Immunosuppressive Agents; Mercaptopurine; Mesalamine; Practice Guidelines as Topic; Prednisolone; Pulse Therapy, Drug; Quality of Life

Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some treatment modalities including corticosteroids have been implicated in growth failure but it is thought mainly to be secondary to uncontrolled disease activity (Motil 1993; Markowitz 1993). Growth is fundamental to the practice of pediatrics, so by taking growth as the primary outcome measure we address issues important to both patients, their families and pediatricians.. To evaluate the effectiveness of the different modalities available for the treatment of childhood Crohn's disease with regard to the reversal of growth failure and the promotion of normal growth.. Searches were made of the following databases using the Collaborative Review Group Search Strategy: EMBASE (1984-2004), MEDLINE (1966-2004), The Cochrane Central Register of Controlled Trials, The Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index. Abstracts from the major gastrointestinal research meetings and references from published articles were also reviewed.. Randomized controlled trials pertaining to children less than 18 years of age with Crohn's disease were selected. Those with growth as an outcome measure were included in the review.. Data extraction and assessment of the methodological quality of each trial was independently reviewed by two reviewers. Only one good quality randomized controlled trial was included in the review and therefore no statistical analysis was possible.. Three randomized controlled trials were identified. One was of good methodological quality (Markowitz 2000). This study looked at the use of 6-mercaptopurine (6-MP) as a steroid sparing agent. No difference in linear growth was observed between the intervention and placebo groups, although the total steroid dose received over the 18 month follow up period was reduced in the group receiving 6-MP. The two remaining randomized controlled trials (Sanderson 1987; Thomas 1993a) consider the use of enteral feeding versus corticosteroids for induction of remission, with height velocity standard deviation score at 6 months as an outcome measure. Although of less rigorous methodological quality, the results of these studies are discussed in detail in the review. In both studies height velocity standard deviation scores were significantly increased in the enteral feeding group compared with the corticosteroid group.. In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.

Topics: Adrenal Cortex Hormones; Antimetabolites; Child; Crohn Disease; Enteral Nutrition; Growth Disorders; Humans; Mercaptopurine; Prednisolone; Randomized Controlled Trials as Topic

Linear growth retardation is a major complication of Crohn's disease that occurs in children. It is related both to undernutrition and to direct effects of the inflammatory process on the growth axis. Enteral nutrition (elemental, semi-elemental or polymeric diet) employed as the sole source of nutrition remains a mainstay of treatment of active Crohn's disease because it corrects nutritional deficits, has anti-inflammatory effects, heals mucosal inflammation and stimulates growth. Conventional corticosteroids have adverse effects on growth and preliminary data suggest that an ileal-release preparation of budesonide may also suppress linear growth. 6-Mercaptopurine (6-MP) and its prodrug azathioprine maintain remission in children with Crohn's disease. These treatments thus have the potential to improve growth velocity and final adult height.

Topics: Adrenal Cortex Hormones; Budesonide; Child; Child Nutritional Physiological Phenomena; Crohn Disease; Diet; Growth Disorders; Humans; Mercaptopurine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Child; Crohn Disease; Drug Administration Schedule; Drug Monitoring; Drug Resistance, Multiple; Gastrointestinal Agents; Growth Disorders; Humans; Immunosuppressive Agents; Induction Chemotherapy; Injections, Subcutaneous; Maintenance Chemotherapy; Male; Mercaptopurine; Remission Induction; Ustekinumab

Topics: Adult; Age of Onset; Antimetabolites; Child; Growth Disorders; Humans; Immune System Diseases; Inflammatory Bowel Diseases; Mercaptopurine

Endocrine dysfunction and damage of the epiphysial growth plates have been reported as late effects of antileukaemic treatment during childhood. It is a common opinion that cranial irradiation (CI) is the most important factor for blunted growth. Accordingly, recent therapeutic strategies in acute lymphoblastic leukaemia (ALL) avoid cranial irradiation. Here we analysed longitudinal data on growth and puberty of 54 children in first complete remission, who were treated with 18 Gy CI or not submitted to radiotherapy. Two chemotherapeutic protocols were compared which were similar during the induction period but differed in the intensity of maintenance therapy. In cranial irradiated patients both in males and females the pubertal growth spurt started at a mean age of 1.2 years (SD: 0.93 years) earlier than controls. Age at diagnosis and age at pubertal growth spurt were significantly correlated (r = 0.35, P = 0.017). Similarly, menarche occurred at a mean age (n = 22) of 12.1 years and was correlated with the age at start of therapy in girls who were treated with 18 Gy CI (r = 0.61, P = 0.01). Adult height was reached spontaneously in 30 patients treated during prepubertal age and in 10 treated shortly before or during puberty. In all prepubertal patients treated for 2-3 years with intensive maintenance therapy blunted growth resulted in a significant loss of -1.85 H-SDS (median, P = 0.0051) compared to height at diagnosis. However, if continuation treatment used only methotrexate and 6-mercaptopurine (i.e. BFM protocol) final height equalled projected adult height, despite 18 Gy CI.. (1) multiagent chemotherapy is of major impact for growth and puberty; (2) 18 Gy cranial irradiation is below the critical dosage responsible for blunted growth; (3) loss in potential growth might be prevented by current CT strategies; (4) onset of puberty depends on age when antileukaemic therapy is applied.

Topics: Adolescent; Age Factors; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Combined Modality Therapy; Cranial Irradiation; Dose-Response Relationship, Radiation; Female; Growth; Growth Disorders; Humans; Longitudinal Studies; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Puberty

We evaluated clinical characteristics and growth in 51 (24 males) long-term survivors of childhood cancer (median follow up 12.7 years). Patients were shorter, had a higher proportion of body fat and higher systolic blood pressure than their controls. The change in relative height during treatment was -0.83 standard deviation score (S.D.S.) in patients with cranial irradiation and -0.32 S.D.S. in patients without cranial irradiation; the figures after treatment were -0.56 and 0.20 S.D.S., respectively. Half (r2 = 0.50) of the variation in growth retardation during therapy could be explained by the cumulative doses of 6-mercaptopurine (6-MP) and vincristine and relative height at diagnosis. Cranial irradiation, increased relative height at diagnosis and young age at diagnosis were significant predictors of growth failure over the total observation period, explaining 43% of the variation. We conclude that long-term survivors of childhood cancer have impaired linear growth, increased body fat mass and elevated systolic blood pressure. Young children who are tall for their age at diagnosis and treated with cranial irradiation have the highest risk of impaired growth after the diagnosis. High doses of 6-MP seem to contribute significantly to growth retardation during therapy.

Topics: Adolescent; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Body Mass Index; Child; Child, Preschool; Cranial Irradiation; Female; Follow-Up Studies; Growth; Growth Disorders; Humans; Infant; Linear Models; Male; Matched-Pair Analysis; Mercaptopurine; Neoplasms; Risk Factors; Survivors

In children treated for acute lymphoblastic leukemia (ALL), catch-up growth occurs after cessation of therapy and not during maintenance therapy. In this study we investigated whether this inhibition of catch-up growth during maintenance treatment is attributable to the influence of chemotherapy or to the influence of corticosteroids.. Forty-six children treated for ALL were included in the study. In 27 patients maintenance therapy comprised vincristine (VCR), prednisone (Pred), or dexamethasone (Dexa) alternated with 6-mercaptopurine (6-MP) and methotrexate (MTX) and 19 patients received maintenance therapy with 6-MP and MTX only. Treatment did not include cranial irradiation.. Statural growth during maintenance treatment was comparable in both groups over the study period of 1.5 years.. Chemotherapy with 6-MP and MTX, and not corticosteroids, is the main factor that prevents catch-up growth from occurring during maintenance therapy for ALL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Growth; Growth Disorders; Humans; Infant; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma

To assess whether children with inflammatory bowel disease (IBD) develop permanent impairment of linear growth, we analyzed records from 48 young adults who had IBD during childhood or early adolescence (Tanner I-III; 11.8 +/- 2.4 years old at diagnosis). All were fully grown (Tanner V; 21.1 +/- 3.0 years) at last examination. Adult heights were predicted from data obtained at or shortly after the diagnosis of IBD by three methods: height for age percentile, the Bailey-Pinneau (BP), and Roche-Wainer-Thissen (RWT) methods. Predicted adult heights were then compared with the actual ultimate height of each subject. Permanent growth failure occurred in 19-35% of subjects, depending upon the method used to assess growth. Overall, 31% (15 of 48) of the subjects had deficits of adult height identified by two or more methods, including 14 of 38 (37%) of those with Crohn's disease but only one of 10 with ulcerative colitis. Age at diagnosis of IBD, age at last examination, age at cessation of linear growth, and site of IBD did not differ between impaired and normal growth groups. Duration of corticosteroid use was longer (p < 0.05) in growth-impaired subjects. In addition, although 60% of all subjects had periods of poor growth that put them in height-for-age percentiles two or more major growth channels below previous percentiles, only 19% remained at these levels upon achieving their final adult heights. Permanent impairment of linear growth leading to clinically meaningful deficits of ultimate adult height is common in patients with IBD in childhood or early adolescence. New therapeutic approaches are needed to address this problem.

Topics: Adolescent; Adrenal Cortex Hormones; Anthropometry; Azathioprine; Body Height; Child; Colitis, Ulcerative; Crohn Disease; Enteral Nutrition; Female; Forecasting; Growth Disorders; Humans; Longitudinal Studies; Male; Mercaptopurine; Parenteral Nutrition; Retrospective Studies

Pubertal growth was studied in 10 girls previously treated for acute lymphoblastic leukemia. The average age at menarche was 12.2 years, which is significantly lower (p less than 0.01) than the expected 13.1 years. Compared with normal girls, these girls showed a subnormal (p less than 0.05) peak height velocity during the second year before menarche. The remaining growth before menarche as well as the total postmenarchal growth was close to the normal average. The average final standing height was 1 SD less than what would be expected from their height 1 year after the cessation of therapy. A relative growth hormone deficiency in combination with early onset of puberty could account for this loss in final height.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Body Height; Child; Child, Preschool; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Female; Growth Disorders; Growth Hormone; Humans; Menarche; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Puberty; Vincristine

Topics: Adolescent; Adrenocorticotropic Hormone; Alpha-Globulins; Antibodies, Antinuclear; Antimetabolites; Azathioprine; Blood Protein Electrophoresis; Calcinosis; Child; Creatine; Dermatomyositis; Electromyography; Exercise Therapy; Female; Fluorescent Antibody Technique; Fructose-Bisphosphate Aldolase; Growth Disorders; Humans; Immunosuppression Therapy; L-Lactate Dehydrogenase; Male; Mercaptopurine; Methotrexate; Middle Aged; Muscles; Prednisone; Remission, Spontaneous; Staphylococcal Infections; Transaminases