ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeA retrospective study was conducted to investigate the prognostic significance of TEL/AML1 fusion resulting from a cryptic t(12;21) in Japanese patients with childhood B-precursor acute lymphoblastic leukemia (ALL).Materials and MethodsLeukemic samples from 144 children with newly diagnosed ALL (104 with CD10-positive B-precursor ALL, 11 with CD10-negative B-precursor ALL, 5 with B-ALL, and 24 with T-ALL) were analyzed by reverse-transcription polymerase chain reaction.ResultsThe frequency of patients with TEL/AML1 was 16% (23 of 144) and all patients with TEL/AML1 also had CD10-positive B-precursor ALL. TEL/AML1 was not found in any samples from the patients with T-ALL, B-ALL, or CD10-negative B-precursor ALL. Among patients with CD10-positive B-precursor ALL, age, initial white blood cell count, and immunophenotype did not differ with TEL/AML1 positivity, although the patients were predominantly male (p < 0.01). Clinical outcomes of 94 patients treated with recent protocols were analyzed. Five of the 21 (23.8%) patients with TEL/AML1 relapsed and 4 of these relapsed > 24 months after diagnosis. Although the overall 5-year survival rate was better among patients with TEL/AML1 fusion transcript than among those without it (87.3 ± 8.7% versus 75.9 ± 5.8%, respectively), the 5-year disease-free survival (DFS) rates of patients with TEL/AML1 fusion transcript and those without it were similar (64.0 ± 13.5% versus 69.1 ± 6.3%, respectively). However, for 57 patients treated with the latest intensive protocol, the 4-year DFS rate was much higher for the patients with TEL/AML1 fusion transcript than for those without it (100.0% v.s. 69.6 ± 8.4%, respectively, p = 0.1472).ConclusionsThis study confirmed that TEL/AML1 gene fusion is the most common genetic event in pediatric ALL in Japan and is restricted to CD10-positive B-precursor ALL. Moreover, it was associated with an improved survival rate among patients treated with intensive therapy. Therefore, these data suggest that the patients with TEL/AML1 may not necessarily be candidates for less aggressive treatment.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeChronic thrombocytopenia is uncommon in children and frequently thought to be secondary to chronic idiopathic thrombocytopenic purpura (ITP), which is considered an immune disorder. However, not all children with chronic ITP respond to immunosuppressive therapy. Platelet survival and megakaryocyte growth were studied to determine if there is a failure of platelet production in children with chronic thrombocytopenia who carry a presumptive diagnosis of chronic ITP.Patients and MethodsIn vitromegakaryocyte growth using a plasma clot system andin vivosurvival of111In-labeled autologous platelets were studied in seven patients (aged 2 days to 17 years at diagnosis; aged 2 to 28 years at time of megakaryocyte study) with chronic isolated thrombocytopenia (range 1,000 to 130,000/μl).ResultsAll seven patients exhibited elevated platelet-associated immunoglobulin G early in the course of their disease and showed normal marrow morphology with normal numbers of morphologically typical megakaryocytes on initial marrow biopsy. Occasional dysplastic-appearing megakaryocytes were noted in three of the seven patients at diagnosis and all patients were noted to have dysplastic megakaryocytes, reduced megakaryocytes, or both during follow-up (range 5 to 16 years). Either morphologic or karyotypic abnormalities indicative of myelodys-plasia subsequently developed in three patients. No patient exhibited any significant megakaryocyte colony growth under basal conditions. In one patient, megakaryocytic colonies significantly increased when grown in the presence of serum from aplastic patients and growth factors (granulocyte-macrophage colony-simulating factor, interleukin-3, and interleukin-6). Erythroid colony growth was markedly deficient in four of five patients studied and myeloid colonies were normal in two of three patients studied. Five of the seven patients underwent platelet survival studies. Platelet survival was < 6 days in the 4 patients with platelet counts < 100,000/μl (range 2 to 60,000/μl; survival range 92 to 137 hours) and was normal in the patient whose platelet count was > 100,000/μl (platelets 132,000/μl; survival 253 hours). All five patients had either overtly low or inappropriately low platelet turnovers (range 100 to 1423 platelets/μl per hour; normal range 1200 to 1600 platelets/μl per hour). The patient with the lowest platelet count and platelet turnover had previously undergone a splenectomy without benefit.ConclusionsMegakaryocyte dysfunction resulting in subnormal production of platelets may play a significant role in the thrombocytopenia noted in some patients who have an isolated thrombocytopenia and a clinical picture that suggests ITP. Determination of platelet turnover may help to identify these patients. These data suggest the presence of a stem cell defect which may progress to myelodysplasia or overt marrow failure in these patients.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeThe association of anti-Braimmunoglobulin G (IgG) platelet alloantibodies with the development of thrombocytopenia in neonates of mothers with autoimmune thrombocytopenic purpura (ITP) is reported.MethodsBetween March 1994 and July 1997, 28 consecutive pregnant women with ITP seen at New York Hospital were screened for platelet-reactive antiglycoprotein (glycoprotein [GP] IIb/IIIa, Ib/IX, and Ia/IIa) antibodies.ResultsThe sera from 6 of these 28 women contained IgGallo-antibodies to GP Ia/IIa directed against the Bra(HPA-5b) antigen. Only three families each had at least one Bra+ and at least one Bra- infant. Platelet typing in these families revealed that the mothers were Brb/b(Bra-) and the fathers were Bra/b(Bra+). Platelet counts <100,000/μl occurred only in 2 of the 3 infants who were Bra+. The platelet counts were significantly lower in the three Bra+ infants compared to the five Bra- infants (p = 0.038).ConclusionPlatelet alloimmunization with anti-Bracan cause neonatal thrombocytopenia in infants-of mothers with ITP. Platelet antibody testing in the pregnant women with ITP is recommended.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeAlthough immune dysfunction is suspected in patients with hemophagocytic lymphohistiocytosis (HLH), the difference between immune dysfunction in patients with familial ery-throphagocytic lymphohistiocytosis (FEL) and familial inheritance-unproved lymphohistiocytosis (FIU) remains unknown. The aim of this study was to determine useful markers to distinguish patients with FEL from those with FIU.Patients and MethodsClinical features and laboratory findings, especially natural killer (NK) cell activity and the relative frequencies of peripheral blood mononuclear cell (PBMC) subsets, and serum levels of interferon-γ and soluble interleukin-2 receptor were compared in 9 patients with FEL and 14 age-matched patients with FIU. Twenty-seven healthy infants served as controls. The treatment and outcome were also compared for patients with FEL and FIU.ResultsComparison between patients with FEL and FIU revealed significantly lower NK activity in those with FEL (p = 0.03) but failed to show any significant differences in PBMC subsets, except that the percentage of CD3+ T cells was higher in patients with FEL (p = 0.02). CD4− and CD8-dominant phenotypes were characteristic findings in both groups of patients, although increased CD19+ B cells were restricted to patients with FIU. NK activity was deficient (< 5%) in four of the seven patients with FEL tested but in only one of eight patients with FIU. By comparison to values for age-matched controls, the percentages of CD3+, CD3+DR+ and CD45RO+ PBMCs in patients with FEL were significantly high (p < 0.05) and those of CD19+ and CD45RA+ subsets were lower than normal. Among patients with FIU, PBMC subsets included significantly reduced CD3+, CD4+, CD45RA+, and CD4+CD45RA+. In this small series, the outcome of patients with FEL and FIU treated with chemotherapy was not significantly different at the time of evaluation.ConclusionsThese results indicate considerable immune heterogeneity among patients with HLH younger than 2 years. Although NK activity was useful but not diagnostic, determination of PBMC subsets and patterns of cytokine expression was not helpful in distinguishing patients with FEL from those with FIU, suggesting that the immune responses characteristic of these diseases may reflect different triggering factors, including viruses. The impact of this immune heterogeneity on patients' outcome remains to be determined.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeThis report describes the incidence of septic shock in pediatric hematology-oncology patients with positive blood cultures and investigates parameters of potential use in early diagnosis of gram-negative (GN) bacteremia and septic shock.PatientsIn a 12-month period, 140 consecutive episodes of septicemia (135 bacterial and 5 fungal) were seen in 100 patients. The absolute neutrophil count (ANC) was > 500/μl in 89 episodes (65%).ResultsSeptic shock developed in patients with positive blood cultures with an overall incidence of approximately 19%. Of the 12 bacteremic patients who required transfer to the intensive care unit, 83% had a GN isolate recovered. The incidence of septic shock was not significantly lower in the group of patients with ANC > 500/μl. Low serum bicarbonate correlated with GN infection in patients with bacteremia.ConclusionsGN organisms were the major cause of septic shock in a group of pediatric hematology-oncology patients with positive blood cultures although they were recovered less frequently than gram-positive organisms. In our study, non-neutropenic patients with indwelling catheters were at approximately the same risk for GN shock as neutropenic patients. Monitoring blood carbon dioxide content may be useful in the early diagnosis of GN infection.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeTo characterize nonleukemic CD10-positive cells in the marrows of children with leukemia in remission or benign conditions.Patients and MethodsSeventeen children with acute leukemia in complete remission, 12 with solid tumors, and 17 with benign blood diseases were included in this study. Bone marrow cells were analyzed by multicolor flow-cytometry and polymerase chain reaction (PCR) to detect immunoglobulin gene rearrangement. The CD10-positive cells were purely sorted and examined by light microscopy and single cell hemopoietic progenitor assay.ResultsIn patients with acute leukemia, CD10-positive cells were present in higher proportion after completion of therapy than during chemotherapy. They were also higher in the patients of preschool age than in the older age group with benign blood diseases and solid tumors. These CD10-positive cells were morphologically compatible with immature lymphocytes but some blast-like cells also occurred in this population. Most CD10-positive cells coexpressed CD19 and HLA-DR, although only 10 to 30% coexpressed CD20 and CD34. Although some CD10-positive cells expressed CD34, they did not make any colonies. PCR analysis did not show monoclonal bands in CD10-positive bone marrow cells in any patients in remission.ConclusionMarrow CD10-positive cells possess immature B-lymphocyte phenotype and are present in higher proportion in the marrows of children with acute leukemia in continuous complete remission after completion of therapy and children of preschool age than school-age children with benign diseases or solid tumors without marrow involvement. The clonality of these cells was excluded by PCR, which is a distinct point from CD10-positive ALL blasts.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeInfants with acute lymphoblastic leukemia (ALL) often enter remission; however, they have a high rate of relapse. To prevent relapse, infants' tolerance of and benefits from early intensive rotating drug pairs as part of therapy were studied.MethodsAfter prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were administered in 30 weeks: A, intermediate dose methotrexate (MTX) and intermediate dose mercaptopurine (MP); B, cytosine arabinoside (Ara-C) and daunorubicin (DNR); C, Ara-C and teniposide (VM-26). Triple intrathecal chemotherapy (Ara-C, MTX, and hydrocortisone) was administered for central nervous system prophylaxis. Continuation therapy consisted of weekly MTX and daily MP for a total of 130 weeks of continuous complete remission.ResultsThirty-three infants (1 year old or younger) with newly diagnosed ALL were treated. Two infants did not respond to induction, I died from sepsis during continuation, I received a bone marrow transplant, and 24 relapsed. Median time to relapse was 39 weeks. The event-free survival rate at 5 years was 17% (standard error × 7.7%). The most significant toxicities occurred during intensification and included fever-neutropenia and bacterial sepsis.ConclusionAlthough early intensive rotating therapy is tolerable, the relapse-free survival rate remains poor for infants treated with the schedule on this protocol.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeOsteoporosis and pathologic fractures are occasionally found in patients with childhood acute lymphoblastic leukemia (ALL). This study was performed to determine the degree of possible osteopenia in long-term survivors of childhood ALL.Patients and MethodsLumbar spine (L2-L4) and femoral neck bone mineral densities (BMDs) (g/cm2) were measured in 29 survivors (aged 12 to 30 years, median 17) of childhood ALL 2 to 20 (median 8) years after discontinuation of chemotherapy. These results were compared with those from 273 healthy controls and expressed as a percentage of the age- and sex-matched control values (mean ± standard deviation).ResultsLumbar and femoral BMDs were significantly reduced in survivors of childhood ALL. Particularly, male gender (lumbar: 91.7 ± 10.4%, p = 0.008; femoral: 91.9 ± 11.3%, p = 0.005) and a history of cranial irradiation (lumbar: 93.0 ± 8.9%, p = 0.005; femoral: 94.4 ± 13.3%, p = 0.03) were associated with low lumbar and femoral BMDs.ConclusionsThe detected deficit in bone density in survivors of childhood ALL may predispose these patients to osteoporotic fractures later in adulthood. A follow-up of BMD in survivors of childhood ALL should facilitate the identification of patients who would require specific therapeutic interventions to prevent further decrease of their skeletal mass and preserve their BMD.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PurposeChildhood cancer and its treatment can affect normal bone accretion. In this study, bone mineral density (BMD) in young adult survivors of childhood cancer is assessed to determine what cancer-related factors, patient characteristics, or treatment-related complications correlate with reductions in BMD.Patients and MethodsThe study population consisted of 40 (24 women) long-term survivors of childhood cancer treated at the Memorial Sloan-Kettering Cancer Center for a solid tumor (n = 16), lymphoma (n = 14), or acute leukemia (n = 10) at a mean age of 12.7 ± 0.96 years and evaluated at a mean age of 25.8 ± 0.7 years. Dual energy X-ray absorptiometry was used to determine BMD of the lumbar spine, femoral neck, and total body and single photon absorptiometry was used to determine BMD of the distal radius.ResultsThe mean BMD standard deviation score (SDS) for the patients was significantly reduced compared to controls at the distal radius (-1.57 ± 0.18, p = 0.0001), femoral neck (-0.68 ± 0.20, p = 0.00014), and total body (-0.33 ± 0.15, p = 0.03) but not at the lumbar spine (-0.22 ± 0.22, p = 0.33). Univariate analysis revealed that gonadal dysfunction (i.e., estrogen or testosterone insufficiency) (p = 0.018) was the only variable that correlated with a reduced BMD.ConclusionYoung adult survivors of childhood cancer have reduced BMD. Because age at study coincides with the normal age of attainment of peak bone mass and peak bone mass is a major determinant of BMD later in life, many of these patients are at increased risk for osteoporosis and fractures.

ISSN:1077-4114    

出版商:OVID    

年代:1998

数据来源: OVID