1 / 37

A Case of Bone Marrow Failure

merv
Télécharger la présentation

A Case of Bone Marrow Failure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

    1. A Case of Bone Marrow Failure And Treatment Dilemmas

    2. 11 yo caucasian male 1 month history of intermittent fevers, fatigue and decreased appetite Intermittent knee pain No weight loss or night sweats Seen in OSH ER and found to have pancytopenia

    3. PMHx: Full term infant – 5 lb No surgeries, no hospitalizations Meds: None Allergies: None

    5. Physical Exam Gen: pale, thin boy Skin: pretibial bruising, no pigment changes Dysplastic, brittle toenails HEENT: nl Lungs: CTA CV: RRR with 1/6 SEM Abd: soft, ND, liver down 1 cm GU: Tanner 1 No LAD Neuro exam normal

    6. Labs

    7. Other Labs ESR – 64 Hepatitis B, Hepatitis C, EBV, CMV neg PNH screen – negative Fanconi screen - negative Bone Marrow – markedly hypocellular marrow with limited normal hematopoiesis Cytogenetics – no abnormalities

    9. DKC Rare disorder Characterized by… cutaneous reticulated hyperpigmentation nail dystrophy premalignant leukoplakia of the oral mucosa progressive pancytopenia

    10. Frequency Most likely underdiagnosed and underreported Approximately 180 cases reported in the literature

    11. Clinical history Mucocutaneous features develop typically between age 5 to 15 years Median age of onset of peripheral cytopenia is age 10 years

    12. Physical findings Cutaneous abnormal skin pigmentation with tan-grey hyperpigmented or hypopigmented macules and patches in a mottled or reticulated pattern typical distribution - upper trunk neck and face Mucosal findings mucosal leukoplakia may become verrucous and ulceration may occur

    13. Physical Findings Nail findings progressive nail dystrophy begins with ridging and longitudinal fissures progressive atrophy thinning and distortion Other findings scalp alopecia hyperhidrosis hyperkeratosis of palms and soles adermatoglyphia

    15. Increased incidence of malignancy Squamous cell carcinoma of skin, nasopharynx, esophagus, rectum, vagina, cervix

    16. Pulmonary complications Fibrosis Abnormalities in the microvascular Presents challenge during BMT

    17. Bone marrow failure Usually occurring in second decade of life Main cause of mortality Median survival following diagnosis with aplastic anemia is approximately 4 years

    18. DC family registry 92 families (as of 1992) 86% of affected patients were male Confirming that the major mutation is X-linked

    20. Mortality 70% of patients die from bone marrow failure or complications at a median age of 16 years 11% died from sudden pulmonary complications 11% died of pulmonary disease in the BMT setting 7% died from malignancy.

    21. Genetics Autosomal Dominant X-linked forms Autosomal Recessive

    22. Autosomal dominant DKC Caused by mutations in the TERC gene Encodes the RNA component of the telomerase complex Mutations have also been found in the TERT gene Encodes the catalytic part of the enzyme telomarase Responsible for elongating and maintaining telomeres

    23. AD DKC Clinical picture is milder than in the X-linked form Patients may show signs of bone marrow failure, but lack the mucocutaneous findings Appears to be anticipation in this form of the disease

    25. X-linked DKC DKC1 encodes dyskerin a nucleolar protein that associates with a class of small nucleolar RNA molecules active pseudouridine synthase also forms part of the telomerase complex Impaired telomerase activity and defective rRNA production most likely both play a role in the X-linked form of the disease

    27. Treatment of Bone Marrow Failure Androgens Immunosuppression Hemopoietic growth factors Bone Marrow Transplant

    28. Bone Marrow Transplant and DKC Only curative measure for bone marrow failure related to DKC Limited experience

    29. Retrospective report of 5 patients with aplastic anemia related to DKC Between 1979 and 1993 All male patients Ages 4-13

    30. Patients

    32. Complications 4 out of 5 patients had vascular lesions and fibrosis involvement of various organs High frequency of bronchopulmonary complications Pts appear to be susceptible to early and late endothelial damage syndromes VOD, TMAS, TTP

    34. How to minimize affects of BMT Minimize endothelial damage Use of heparin or prostaglandin E1 Modification of conditioning regimen Avoidance of radiation Improved supportive Care Surveillance of the unusual complications

    35. Report of 2 children with DKC and severe aplastic anemia Underwent successful MUD HSCT Over 1 year out with minimal transplant related mortality

    36. Conditioning Regimen Fludarabine 30mg/m2/day from day –10 to day –5 Cyclophosphamide 60mg/kg/day from day –6 to day –5 ATGAM from day –4 to day –1 GVHD prophylaxis – cyclosporine and prednisone

    37. What to do? Cure means BMT HLA -typed he and his family Conditioning regimen of Campath, Fludarabine, and Melphalan Started on oral cyclosporine Considering use of androgens Increased immunosuppression and/or Erythropoeitin and neupogen

More Related