以高钙血症和骨质改变为首发表现的儿童急性淋巴细胞白血病1 例报告

目的探讨以骨质改变和高钙血症为首发表现的儿童急性淋巴细胞白血病(ALL)的临床特点及诊治。方法回顾分析1例以骨质改变和高钙血症为首发表现的儿童B细胞ALL的临床资料。结果患儿,男性,6岁5个月,以腹痛起病,初期检查发现骨质改变及高钙血症,后确诊ALL。采用CCLG-ALL-2015方案化疗,同时加用伊马替尼口服,目前已获得缓解。结论高钙血症和骨质改变可以是B细胞ALL首发表现。     

A case of acute lymphoblastic leukemia presenting as severe hypercalcemia

A 9-year-old girl presented at the Pediatric Emergency Department with an acute onset of gastrointestinal symptoms due to hypercalcemia. Despite the absence of circulating blast, bone marrow biopsy was diagnostic of acute lymphoblastic leukemia. The hypercalcemia was initially treated with intravenous hydration and furosemide, and later on with bisphosphonates. However, the serum calcium levels normalized only after the beginning of specific chemotherapy. Hypercalcemia represents an emergency in children, and acute leukemia must be considered in its differential diagnosis, even when there are no circulating blasts.     

Remission maintenance of adult acute lymphoblastic leukemia

This report describes the results of a study of central nervous system (CNS) prophylaxis and combination chemotherapy for the maintenance of remission in adult acute lymphoblastic leukemia. Adults with acute lymphoblastic leukemia who achieved complete remission were treated with 2,400 rads cranial irradiation and intrathecal methotrexate for CNS prophylaxis followed by continuation systemic chemotherapy with oral methotrexate, 6-mercaptopurine and cyclophosphamide. There were no CNS relapses following treatment. One-half of the patients relapsed within 11 months, with 5 patients remaining in remission for 27+ to 31+ months. The toxicity was acceptable with no treatment-related deaths. This regimen is capable of producing long remissions in a significant proportion of adults with acute lymphoblastic leukemia and appears to be effective in reducing the incidence of CNS relapse. It has the additional advantage of ease of administration and can be largely administered in the community.     

Recent progress in the treatment of infant acute lymphoblastic leukemia

Treatment of infants with acute lymphoblastic leukemia (ALL), especially those with mixed lineage leukemia (MLL) rearrangement (MLL‐r), which account for approximately 80% of cases, is still a major challenge for pediatric hematologists and oncologists worldwide. Continuing efforts by collaborative clinical study groups in Europe, North America, and Japan have rescued approximately half of the MLL‐r ALL patients with intensive chemotherapy with or without allogeneic hematopoietic stem cell transplantation. Recent progress has clarified the unique mechanism of MLL‐r ALL: the aberrant methylation and histone modifications via DOT1L and other related molecules by MLL fusion proteins lead to leukemogenetic gene expression, thus to overt leukemia. In order to overcome this dismal subtype of ALL, novel targeted therapy based on leukemia biology is urgently needed. Due to the extreme rarity of the disease, collaboration between the study groups in Europe (Interfant), North America (Children's Oncology Group), and Japan (Japanese Pediatric Leukemia/Lymphoma Study Group) is under way.     

Childhood acute lymphoblastic leukemia in the age of genomics

The recent sequencing of the human genome and technical breakthroughs now make it possible to simultaneously determine mRNA expression levels of almost all of the identified genes in the human genome. DNA "chip" or microarray technology holds great promise for the development of more refined, biologically-based classification systems for childhood ALL, as well as the identification of new targets for novel therapy. To date gene expression profiles have been described that correlate with subtypes of ALL defined by morphology, immunophenotype, cytogenetic alterations, and response to therapy. Mechanistic insights into treatment failure have come from the definition of mRNA signatures that predict in vitro chemoresistance, as well as differences between blasts at relapse and new diagnosis. New bioinformatics tools optimize data mining, but validation of findings is essential since "over-fitting" the data is a common danger. In the future, genomic analysis will be complemented by evaluation of the cancer proteome.     

Severe mercaptopurine-induced hypoglycemia in acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia maintenance chemotherapy includes mercaptopurine, a purine analog with uncommon side effects, that can be life-threatening. We describe a 7-year-old female patient with ALL that presented with altered state of consciousness after maintenance chemotherapy with methotrexate and 6-mercaptopurine, due to severe hypoglycemia with metabolic acidosis. She initiated metabolic corrections with rapid resolution of symptoms. Hypoglycemia secondary to 6-mercaptopurine is a rare and transient side effect. The cause effect relation is difficult to establish, leading to underdiagnosis. Hypoglycemia is preventable without compromising maintenance therapy efficacy.     

Acute nonlymphoblastic leukemia in children treated for acute lymphoblastic leukemia with an intensive regimen including teniposide

Some cases of conversion from acute lymphoblastic leukemia (ALL) to acute nonlymphoblastic leukemia (ANLL) at relapse have been reported recently. We report three cases initially diagnosed as having ALL and showing morphological, cytochemical, and immunophenotypic features of ANLL at relapse (lineage switch). Conversion was observed among 14 patients who developed bone marrow relapse while undergoing intensive treatment with our ALL protocol, which includes teniposide, and that had been administered to 62 patients. The three cases converted at first relapse, with a mean time of 20 months (13–29 months). Clinical and immunologic characteristics of T-cell leukemia were present in one patient. Changes documented in cytogenetic studies are discussed. The underlying mechanisms for the lineage switch remain unclear as does its relation with mixed lineage leukemias, but we believe that drugs employed in our therapy protocol could have had an influence on this conversion.     

CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemia

A 9-month-old infant presented with hypercalcemia and lytic bone lesions. Suspicion for malignancy led to a bone marrow examination, which showed replacement of the marrow by a small round blue cell infiltrate. Flow cytometric analysis of these cells showed an unusual immunophenotype in that these cells were dim CD45, HLA-DR, and CD10 positive, but CD19, CD20, CD79a, and CD34 negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic leukemia (ALL). He received supportive treatment with hydration and pamidronate, but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL was established, the patient was treated with an infantile ALL chemotherapeutic regimen and the hypercalcemia resolved. This case highlights the usefulness of immunoglobulin gene rearrangement studies in atypical cases of ALL.     

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??Ph-like acute lymphoblastic leukemia??ALL?? is a recently defined subgroup of leukemia with gene expression profile and prognosis similar to Ph chromosome positive ALL. Genomics study has revealed Ph-like ALL is associated with mutations happening to cytokine receptor?? tyrosine kinases and Ras family. Kinase inhibitors targeting the mutated molecules have already benefited several patients with Ph-like ALL.     

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug‐supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol. There were no adverse events related to the pegaspargase during desensitization, and all patients who were checked had asparaginase serum levels above the threshold of 0.1 IU/mL at 7 to 14 days after pegaspargase therapy.     

Unusual cytogenetics in a case of acute lymphoblastic leukemia

The cytogenetics in the study of a patient with acute lymphoblastic leukemia are presented. Initially, a large proportion of both unstimulated and phytohemagglutinin (PHA)-stimulated blood mitoses showed an abnormal karyo-type with a 7;12 translocation and a trisomy 19. At the time of relapse, a PHA-stimulated culture showed the clonal abnormality as well as dicentric chromosomes in normal cells, the latter possibly resulting from treatment.     

Vincristine disposition in children with acute lymphoblastic leukemia

Vincristine (VCR) has been widely used to treat childhood malignancies for over thirty years, but its plasma disposition has not yet been well-defined. Therefore, we conducted a pharmacokinetic study of VCR in 17 children with acute lymphoblastic leukemia (ALL) receiving the first dose of VCR. A new high-performance liquid chromatographic assay was used for the measurement of VCR in plasma. A two-compartment pharmacokinetic model was fit to the data by nonlinear least-squares regression. Estimated pharmacokinetic parameters were highly variable; mean (S.D.) volume of distribution at steady-state was 360 (176) L.m^?2; total body clearance was 431 (238) ml. min^?1.m^?2, and elimination half-life was 823 (390) min. These results were compared to data from eight adults with lung cancer. Mean volume of distribution in adults and children were similar, but VCR clearance was significantly larger in children (P = 0.01), resulting in a significantly longer elimination half-life in the adults (P < 0.01). We conclude that administration of a standard dosage of VCR to children with ALL results in a highly variable systemic drug exposure, which may have implications for the oncolytic effect and/or toxicity in individual patients. Comparison of data from children and adults suggests that VCR elimination rate is a function of age; this could account for more severe neurotoxicity in older patients. However, it cannot be excluded that differences between the children and adults may be due to other variables than age. Future studies should focus on the possible influence of multidrug resistance modulating agents on VCR pharmacokinetics and on pharmacokinetic-pharmacodynamic relationships in individual patients. © 1995 Wi1ey-Liss Inc.     

T-cell acute lymphoblastic leukemia relapsing as acute myelogenous leukemia

We present the unusual case of a 16-year-old girl with T-cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease. Whether the AML represented a relapse with lineage switch of the original immature T-cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers. This report suggests that a subset of CD7+ T-cell leukemias without mature T-cell antigens (CD4-, CD8-) are minimally differentiated and can relapse as AML.     

Intrauterine monoclonal origin of neonatal concordant acute lymphoblastic leukemia in monozygotic twins

We report detailed immunological, cytogenetic and molecular evidence for complete identity of the leukemic cell populations in monozygotic female twins with concordant leukemia diagnosed at two months of age. Both infants had early pre-B acute lymphoblastic leukemia with the (11;19)(q23;p13) chromosomal translocation. A common clonal origin of leukemia in these infants was suggested by the finding of identical oligoclonal heavy chain immunoglobulin gene rearrangements. Leukemic cell DNA was examined for 11q23 rearrangements by Southern blotting and restriction fragments of identical size were found in the two cases, in contrast to the diversity of rearrangements observed in other unrelated and nontwinned control infants with t(11;19)(q23;p13). Similar restriction fragments were absent in blood mononuclear DNA from both parents, liver tissue from one twin and remission bone marrow of the other, indicating that the 11q23 rearrangement was acquired and not inherited as a chromosomal abnormality or polymorphism. These findings provide a definitive evidence for intrauterine single cell origin, with twin to twin transmission, of concordant leukemia in this infant twin pair. © 1995 Wiley-Liss, Inc.     

Acute lymphoblastic leukemia in patients with Down syndrome with a previous history of acute myeloid leukemia

Patients with Down syndrome (DS) are predisposed to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in early and later childhood, respectively, but rarely experience both. We herein discuss four patients with DS with ALL and a history of AML who were treated with various chemotherapies, one of whom later received a bone marrow transplantation. Three patients survived and remain in remission. One patient died of fulminant hepatitis during therapy. No common cytogenetic abnormalities in AML and ALL besides constitutional +21 were identified, indicating that the two leukemia types were independent events. However, the underlying pathomechanism of these conditions awaits clarification.     

T-cell acute lymphoblastic leukemia following therapy of rhabdomyosarcoma

Multiple studies have documented an increased risk of secondary malignancies in patients receiving alkylating agents. Secondary leukemia following chemotherapy accounts for about 20% of all secondary neoplasms; most are acute nonlymphocytic. Secondary acute lymphoblastic leukemia has rarely been reported in either adult or childhood cancer. We report the development of acute T-cell lymphoblastic leukemia in a child following successful treatment of a paravertebral embryonal rhabdomyosarcoma (ERS). Southern blot analysis of DNA extracted from the T-cell lymphoblasts, using probes homologous to loci on the short arm of chromosome 11; P-calcitonin, P40.1 and H-ras, did not demonstrate the chromosomal loss of heterozygosity (LOH), a common feature of embryonal rhabdomyosarcoma. The data presented support the assumption that de novo leukemia emerged following treatment of the primary malignancy. © 1992 Wiley-Liss, Inc.