Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.
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PMID:Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes. 818 40

Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m2), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m2). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n = 1), interstitial pneumonitis (n = 1) and veno-occlusive disease of the liver (n = 1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69 +/- 15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well.
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PMID:Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children. 911 98

A patient with refractory anemia with an excess of blasts in transformation developed pancytopenia and a concurrent interstitial pneumonia 110 days after allogeneic bone marrow transplantation. Bone marrow examination showed 0.4% giant proerythroblasts and 86.2% granulocytes, some of them large with a bizarre configuration and the others of normal size. Serum folate level was found low, 0.6 ng/ml. Immunocytochemistry with a B19-specific monoclonal antibody MAB8292 revealed B19 capsid antigen only in erythroblasts and large, bizarre granulocytes, but not in granulocytes of normal size. In situ hybridization of bone marrow cells using digoxigenin-labeled DNA probes detecting parvovirus B19 also demonstrated positive signals in 8.5% of marrow cells. Parvovirus B19 DNA was isolated from the serum and the bronchoalveolar lavage fluid of this patient by the polymerase chain reaction. These findings suggest that neutropenia may be caused by an involvement with parvovirus B19 though a deficiency of folic acid may have in part contributed to the genesis of neutropenia in the patient. The relevance of parvovirus B19 to the interstitial pneumonia remains unclear.
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PMID:Human parvovirus B19 capsid antigen in granulocytes in parvovirus-B19-induced pancytopenia after bone marrow transplantation. 997 42