BACKGROUND: Precursor T-cell acute lymphoblastic leukemia (T-ALL) has worse prognosis than B-cell ALL. We aimed to evaluate prognostic variables in pediatric T-ALL. METHODS: Medical records of 36 T-ALL patients (27 males and 9 females; median age at diagnosis, 10.6 years) diagnosed and treated at Asan Medical Center from 2001 to 2017 were reviewed. Six patients (16.7%) had early T-cell precursor ALL (ETP-ALL). Most patients received the Children's Cancer Group-1882 (CCG1882) or Korean multicenter high risk ALL (ALL0601) protocols and prophylactic cranial irradiation. Clinical features at presentation, response to therapy, and treatment outcomes were analyzed. RESULTS: The six patients with ETP-ALL and 17 of 30 with non-ETP-ALL received CCG1882 or ALL0601 chemotherapy. Three patients, including two with ETP-ALL, did not achieve complete remission after induction. Rapid early response during induction was achieved by 26 patients. Five year overall survival (OS) and event free survival (EFS) rates were 71.4% and 70.2%, respectively. ETP-ALL and slow early response during induction were significant adverse prognostic factors, while hyperleukocytosis at diagnosis was not. CCG1882/ALL0601 chemotherapy resulted in superior survival (OS: 78.9%, EFS: 73.3%) compared with CCG1901 chemotherapy (OS: 64.3%, EFS: 64.3%), and patients undergoing prophylactic cranial irradiation had superior EFS to non-radiated patients. CONCLUSION: A high risk ALL protocol with intensified post-remission therapy, including prophylactic cranial irradiation, conferred T-ALL survival outcomes comparable with those of Western studies. Further treatment intensification should be considered for patients with ETP-ALL and slow induction responders. Additionally, CNS-directed treatment intensification, without prophylactic cranial irradiation, is needed.
B-Lymphocytes ; Chungcheongnam-do ; Cranial Irradiation ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Female ; Humans ; Male ; Medical Records ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor Cells, T-Lymphoid ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; T-Lymphocytes*

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and may exhibit central nervous system (CNS) involvement. Advances in chemotherapy and effective CNS prophylaxis have significantly decreased the incidence of CNS relapse of ALL to 5-10%. Here, we report the case of a patient with isolated CNS relapse of standard risk group pre-B-cell type ALL in an 11-year-old girl, relapsed 3 years after successful completion of chemotherapy. An 11-year-old girl visited our hospital complaining of headache, dizziness, vomiting, and visual field defects. Neurological examination revealed left-side homonymous hemianopsia. Brain magnetic resonance imaging showed a large irregular dural-based sulcal hematoma in the right parietal and occipital lobes. Surgery to remove the hematoma revealed the existence of hematopoietic malignancy after pathologic evaluation. Bone marrow biopsy was subsequently performed but showed no evidence of malignancy.
Biopsy ; Bone Marrow ; Brain ; Central Nervous System* ; Child ; Dizziness ; Drug Therapy ; Female ; Headache ; Hematologic Neoplasms ; Hematoma ; Hemianopsia ; Humans ; Incidence ; Leukemia ; Magnetic Resonance Imaging ; Neurologic Examination ; Occipital Lobe ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor Cells, B-Lymphoid ; Rabeprazole ; Recurrence* ; Visual Fields ; Vomiting

B-Lymphocytes ; Child ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; Precursor Cells, B-Lymphoid ; pathology

Adult ; China ; Humans ; Leukemia, Lymphoid ; diagnosis ; therapy ; Prognosis

OBJECTIVETo explore clinical and experimental features of 28 cases of childhood acute myeloid leukemia (AML) with 11q23/MLL gene rearrangements.

METHODSKaryotypes of 234 cases of de novo childhood AML were analyzed using short-term culture of bone marrow cells and R-banding. The fusion transcripts involving MLL gene and partial tandem duplication of MLL (MLL-PTD) were detected by multiple reverse transcription polymerase chain reaction (RT-PCR) assay. Two cases with 11q23 translocation by karyotypic analysis but with negative result of multiple RT-PCR were studied with MLL-dual-color fluorescence in situ hybridization (D-FISH).

RESULTSR-banding karyotypic analysis has revealed 20 cases with 11q23 translocation (14 cases with M5, 4 cases with M4, 2 cases with M2), including 12 cases with t(9;11)(p22;q23), 3 cases with t(1;11)(q21;q23), 2 cases with t(6;11)(q27;q23), 1 case with t(11;19)(q23;p13), 1 with t(5;11)(q31;q23), and 1 with t(X;11)(q24;q23). Eighteen cases with 11q23 translocation having fusion transcripts involving MLL genes were confirmed with multiple RT-PCR; 2 cases showed negative results, but they were confirmed to have MLL rearrangements by D-FISH. MLL-PTD was also detected in 8 cases (4 cases M5, 2 cases M4, M2 and M6, one case each) from the other childhood AML cases. The total incidence of 11q23/MLL gene rearrangements was 11.97% (28/234), and most of patients(85.7%, 24/28) were M4/M5. The complete remission (CR) rate after treatment for the 28 cases with MLL rearrangements was 53.8%, the difference was significant by statistics (P< 0.05) compared with 90.5% for the control group (M4/M5 childhood AML with other karyotypic abnormalities or normal karyotype). Of them, 2 cases receiving intensive chemotherapy survived for 81 and 66 months, respectively, 4 cases receiving allogeneic stem cell transplantation survived for 21, 20, 16 and 11 months, respectively, and are still alive with CR. The medium survival (MS) time for 28 cases with 11q23/MLL rearrangements was 11 months, whereas the MS for control group was 15 months. The difference was not statistically significant(P> 0.05).

CONCLUSIONThe 11q23/MLL rearrangements is highly correlated with the occurrence of monocytic leukemia (M4 and M5). The 11q23 translocation and MLL-PTD are mutually exclusive, though both are indicative of poor prognosis. Intensive chemotherapy and allogeneic stem cell transplantation may ameliorate the clinical outcome. Multiple RT-PCR combined with karyotypic analysis and D-FISH are useful for screening the 11q23/MLL rearrangements in childhood AML.

Adolescent ; Child ; Child, Preschool ; Chromosomes, Human, Pair 11 ; Female ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; mortality ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Remission Induction ; Translocation, Genetic ; Treatment Outcome

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.
Adult ; Antineoplastic Agents/therapeutic use ; Base Sequence ; Breast Neoplasms/drug therapy/radiotherapy ; *Chromosomes, Human, Pair 11 ; *Chromosomes, Human, Pair 19 ; Combined Modality Therapy ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Gene Rearrangement ; Humans ; Immunophenotyping ; Karyotyping ; Molecular Sequence Data ; Myeloid-Lymphoid Leukemia Protein/*genetics ; Neoplasm Proteins/*genetics ; Nuclear Proteins/*genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics ; Sequence Analysis, DNA ; Tamoxifen/therapeutic use ; Transcription Factors/*genetics ; *Translocation, Genetic

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1x10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0x10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.
Antibiotics, Antineoplastic/therapeutic use ; Blood Cell Count ; Bone Marrow/pathology ; Breast Neoplasms/*drug therapy/radiotherapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/therapeutic use ; Cytogenetic Analysis ; Epirubicin/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; Myeloid-Lymphoid Leukemia Protein/*genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*etiology/genetics/pathology ; *Translocation, Genetic

This study was aimed to analyze the clinical and cytogenetic characteristics of acute leukemia with 11q23/mll rearrangement and explore the reasonable therapeutic principles. Characteristics in general situation, morphology, immunology, molecular biology, cytogenetics, treatment and overall survival of 36 cases of acute leukemias with mll gene rearrangement were studied and analyzed. The results showed that 36 cases with mll gene rearrangement were found positive (7.2%) in 494 patients with acute leukemia. Among the 36 cases of mll rearrangement positive, 32 cases were diagnosed as acute myeloid leukemia (AML) with myeloid antigen expression, of which 5 cases expressed lymphoblastic differentiation antigen; 4 cases were classified as B-lineage acute lymphoblastic leukemia (ALL), of which non-lineage myeloid expression pattern were found in 3 cases. In 29 out of 36 cases (80%) the clonal chromosomal aberration were detected, of which chromosome 11 aberration were observed in 22 cases. All patients received chemotherapy with a total response rate of 47.2%. Of the responded patients, 10 cases relapsed within 6 months, with a recurrence rate of 40%; 9 cases received hematopoietic stem cell transplantation (HSCT), 7 cases of which survived after transplantation. The median survival time of 36 cases was 16 months (range 2 - 46) and their 2-year overall survival rate was 41.4%. The 2-year overall survival rate of 9 patients who received HSCT was 87.5%. It is concluded that acute leukemia patients with mll gene rearrangement show poor response to chemotherapy, high recurrence rate and poor prognosis. Hematopoietic stem cell transplantation may be a reasonable treatment principle to improve these patients' survival situation.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; Histone-Lysine N-Methyltransferase ; Humans ; Infant ; Leukemia ; classification ; diagnosis ; genetics ; therapy ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; therapy ; Male ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; therapy ; Prognosis ; Survival Rate ; Young Adult

OBJECTIVETo investigate whether there were differences in the clinical characteristics, cytogenetic characteristics, immunophenotype and prognosis in children with B cell type acute lymphoblastic leukemia (B-ALL) carrying different fusion genes.

METHODSThe research included 80 children with B-ALL from Peking University People's Hospital between March 2006 and December 2008. Eighteen children were positive for TEL/AML1, 14 for E2A/PBX1, 11 for BCR/ABL,and 2 cases for MLL/AF4, and 35 cases were negative for all of the 4 fusion genes. Data including clinical characteristics, morphology, immunophenotype and cytogenetic characteristics were collected, and the disease-free survival (DFS) was evaluated. The children were followed up until April 2009.

RESULTSIn the 18 children with TEL/AML1+B-ALL, 66.7% were younger than 5 years old. They had low tumor load. FAB-L2 morphology was commonly observed, but t(12;21) was often absence in these children. Up to now,17 children who survived were disease-free. In the 14 children with E2A/PBX1+B-ALL, the majority were female. Thirteen children showed FAB-L1 morphology. Twelve children showed pre-B-ALL immunophenotype. The EFS was close to 80%. In the 11 children with BCR/ABL+B-ALL, 10 children showed common B type immunophenotype. FAB-L1 and FAB-L2 morphology was found in 4 children respectively. The DFS was less than 20%. Two children with MLL/AF4 positive B-ALL had high tumor load. Their morphologic diagnosis was FAB-L1. Both showed the Pro-B-ALL immunophenotype. One child discontinued treatment at the early stage of chemotherapy, and the other child survived disease-free until now.

CONCLUSIONSThe B-ALL children with different fusion genes have different clinical characteristics, immunophenotypes and prognosis.

Adolescent ; Child ; Child, Preschool ; Core Binding Factor Alpha 2 Subunit ; genetics ; Female ; Gene Fusion ; Homeodomain Proteins ; genetics ; Humans ; Immunophenotyping ; Infant ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; immunology

Precursor B-cell lymphoblastic lymphoma is a rare type of non-Hodgkin's lymphoma seen exclusively in children and young adults. The neoplasm is rare in old age. We report a case of a 58-year-old male, who presented with variable-sized, erythematous to brownish papules and plaques on the scalp and face. There were no other symptoms. Pathological examination showed non-specific, sparse superficial and deep perivascular lymphocyte infiltration. We diagnosed the condition as rosacea and prescribed 100 mg of minocycline per day for 10 days. When he was seen 10 days later, his skin lesions were aggravated and re-biopsy was completed. Histopathology revealed diffuse infiltrates of small to medium-sized lymphoid cells with blastic nuclear chromatin and a high mitotic rate. Immunohistochemical study showed that infiltrated lymphoid cells were precursor B-cell type. Physical examination and staging work-up revealed extensive involvement of lymphoma in bilateral kidney, heart, pancreas, axial and proximal appendicular bones, scalp and cervical lymph node. The patient is being treated with combination chemotherapy.
Child ; Chromatin ; Drug Therapy, Combination ; Heart ; Humans ; Kidney ; Lymph Nodes ; Lymphocytes ; Lymphoma ; Lymphoma, Non-Hodgkin ; Male ; Middle Aged ; Minocycline ; Pancreas ; Physical Examination ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cells, B-Lymphoid ; Rosacea ; Scalp ; Skin ; Young Adult