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[Two patients with acute promyelocytic leukemia whose relapse was noted by cytodiagnosis of middle ear discharge].

Patient 1 was a 36-year-old male and diagnosed as APL in April 1989, and treated with BHAC-DMP and BHAC-AMP. In January 1990, a diagnosis of exudative otitis media was made, but intractable. In June, left facial paralysis appeared and cytodiagnosis of the discharge from the middle ear confirmed leukemic cells. Otitis media and facial paralysis improved after high dose Ara-C, but developed again 5 months later. The condition improved after high dose Ara-C and irradiation of the temporal bones. In September 1992, he died of recurrence but no aggravation in facial paralysis or otitis media. Patient 2 was a 24-year-old female and diagnosed as APL in July 1989, and treated with BHAC-DMP. In May 1990, exudative otitis media was appeared. In July, recurrence was observed but improved by high dose Ara-C. In October, otitis media was aggravated again, and cytodiagnosis confirmed leukemic cell infiltration. She was treated with high dose Ara-C and irradiation of the temporal bones, then achieved complete remission. Maintenance therapy was continued until August 1992, she has been alive. When exudative otitis media developed during the course of leukemia, cytodiagnosis of the discharge from the middle ear should be performed. High dose Ara-C and irradiation of the temporal bone were effective.

Adult↗

[An allogeneic bone marrow transplantation for chronic myelocytic leukemia with a large extramedullary tumor in the pelvic cavity].

A 16-year-old girl developed a pain and paresis in the right hip joint in April 1994. Abdominal CT scan revealed hepatosplenomegaly and large tumor mass (6 x 7 x 13 cm) invading the right psoas muscle in the pelvic cavity. Laboratory data disclosed marked granulocytosis, the presence of Ph1 translocation and bcr-abl rearrangement, thus a diagnosis of CML was made. The tumor was shown to be consisted of granulocytes at all stages of development by a fine needle aspiration cytology. According to the criteria of IBMTR, the disease was classified as accelerated phase solely because the sum of myeloblasts and promyelocytes exceeded over 20%. The patient was treated with hydroxycarbamide, 6MP and dexamethasone, and marked reduction of the tumor mass was observed. Then an allogeneic BMT was performed from her HLA- identical brother on August 1994. She did not develop clinically significant symptoms except for grade I skin GVHD. The tumor was completely disappeared after the BMT as assessed by the abdominal CT scan. No cytological and chromosomal relapse has been observed for 20 months after the BMT.

Adolescent↗

Low incidence of CNS relapse with cranial radiotherapy and intrathecal methotrexate in acute lymphoblastic leukemia.

OBJECTIVES: To assess the incidence of isolated central nervous system (CNS) relapses in patients of acute lymphoblastic leukemia (ALL) treated with a protocol containing cranial irradiation and intrathecal methotrexate as CNS directed therapy. DESIGN: Prospective non randomized study. SETTING: Department of Medical Oncology, Tata Memorial Hospital. SUBJECTS: 623 children of ALL on MCP 841. METHODS: CNS relapse was diagnosed, if upon examination of the CSF, more than 50 cells/microliter were observed, or a count of 5 cells which were unequivocally lymphoblasts. RESULTS: The incidence of isolated CNS relapse was 1.75% with the use of this treatment. Age, sex, white blood cell count, platelet count, lactic dehydrogenase and immunophenotyping were not significantly related to isolated CNS relapse. CONCLUSION: A low incidence of isolated CNS relapse demonstrates the adequacy of the presymptomatic CNS therapy.

Adolescent↗

[Acute myeloid leukemia with monosomy 7 accompanied by central diabetes insipidus].

A 27-year-old female was diagnosed as having atypical aplastic anemia in 1979 because of hypercellular bone marrow with abnormal erythroblasts and megakaryocytes. Afterward the diagnosis was corrected to myelodysplastic syndrome (RA) due to the reevaluation of the bone marrow smears. In March, 1995, thirst and polyurea occurred. In April, 1995, bone marrow aspiration biopsy showed the proliferation of atypical blasts (28%), and two months later, the number of the blasts increased (30%) and leukemic progression was noticed. Only 0.5 percent of the blasts showed weak peroxidase activity, and most of the blasts had CD13, CD33 and several adhesion molecules as CD11a, CD11b, CD44, CD54 and CD56. Karyotype of the bone marrow cells was 45, XX, -7. Her polyurea was caused by central diabetes insipidus. She was also complicated by pleuritis, colon ulcer, sinusitis and hypothalamic dysfunction. The etiology of these signs was due to the leukemic cell infiltration. She died despite of receiving multi-drug chemotherapy.

Adult↗

[Masquerading syndromes].

Masquerade syndromes comprise a number of diseases imitating as to their clinical picture inflammation of the eye. These diseases comprise also malignant tumours. The authors present three patients where intraocular tumours (lymphoma, leukaemia, melanoma of the choroid) reminded of chronic uveitis.

Aged↗

Unusual ocular findings in children's acute leukemia cases.

The most frequent ocular findings in acute leukemia cases of children and two of our own observations are presented in this study. Emphasized are all difficulties in fixing the diagnosis and the necessity of close cooperation between ophthalmologist, pediatrist and radiologist to prevent the irreversible ocular changes.

Acute Disease↗

Leukemia cutis as the initial manifestation of acute nonlymphocytic leukemia in a young child.

A 15-month-old boy was well except for asymptomatic, erythematous, wheal-like papuloplaques, macules, and nodules on his face and four extremities. It was misdiagnosed by a pediatrician and treated as urticaria for six months. Later, he was sent to our hospital for evaluation of prolonged fever. Acute nonlymphocytic leukemia (M5) with leukemia cutis was diagnosed by results of hematologic examination and examination of a skin biopsy specimen. After one course of chemotherapy, all of the skin lesions completely resolved and had not recurred. Five months after acute nonlymphocytic leukemia was diagnosed, bone marrow relapse and central nervous system involvement were noted.

Humans↗

Development of acute lymphoblastic leukemia and myeloproliferative disorder in transgenic mice expressing p210bcr/abl: a novel transgenic model for human Ph1-positive leukemias.

The Philadelphia (Ph) chromosome can be detected in chronic myelogenous leukemia (CML) and a significant number of acute lymphoblastic leukemia (ALL) cases. Generation of p210bcr/abl, a chimeric protein with enhanced kinase activity, is thought to be involved in the pathogenesis of these diseases. To elucidate the biological properties of p210bcr/abl and to create an animal model for human Ph1-positive leukemias, we generated transgenic mice expressing p210bcr/abl driven by the promoter of the tec gene, a cytoplasmic tyrosine-kinase preferentially expressed in the hematopoietic lineage. The founder mice showed excessive proliferation of lymphoblasts shortly after birth and were diagnosed as suffering from ALL based on surface marker and Southern blot analyses. Expression and enhanced kinase activity of the p210bcr/abl transgene product were detected in the leukemic tissues. In contrast, transgenic progeny exhibited marked granulocyte hyperplasia with thrombocytosis after a long latent period and developed myeloproliferative disorders (MPDs) closely resembling human CML. Expression of p210(bcr/abl) mRNA in the proliferating granulocytes was detected by RT-PCR. In particular, one MPD mouse showed remarkable proliferation of blast cells in the lung, which might represent an extramedullar blast crisis. The results demonstrate that the expression of p210bcr/abl in hematopoietic progenitor cells in transgenic mice can contribute to two clinically distinct hematopoietic malignancies, CML and ALL, indicating that this transgenic system provides a novel transgenic model for human Ph1-positive leukemias.

Animals↗

[The data-base including digitized morphologies for clinical testing of bone marrow samples using personal computer].

Clinical testing of bone marrow is essential for diagnosis and treatment of hematopoietic disorder. It is sometimes difficult to provide an accurate morphological explanation of bone marrow cells in the reports. Various methods, such as detailed descriptions or sketches of the cells have been attempted to accurately describe the results to clinicians. However, these descriptions and sketches may vary depending on the individual. To resolve this problem, a data-base including digitized microscopic examinations using a personal computer for tested bone marrow samples has been developed. This system enables accurate reporting of cellular morphology by printing out colored figures. Moreover, chronological data may be easily displayed and reviewed on the screen. To assess those functions and the quality of print outs showing cellular morphologies, a questionnaire survey evaluating this system was conducted. As a result, a fairly good assessment was given to the print outs showing various morphologies including leukemic cells, infiltrated tumor cells and some cytochemical staining methods (peroxidase, esterase and periodic acid Schiff reaction). However, a few respondents suggested that expression color in print outs of minute morphologies such as chromatin strands, nucleoli and a few azurophil granules were incomplete. As for data-base functions, responses to the questionnaire were fairly good. In conclusion, this attempt is very useful and practical for clinical testing of bone marrow samples.

Bone Marrow Cells↗

[Acute promyelocytic leukemia relapse as leukemia cutis shortly after complete remission with all-trans retinoic acid].

A 56-year-old man was admitted to our hospital in September, 1996. Chromosomal translocation (15; 17) and a PT-PCR study for PML-RAR alpha mRNA were positive in bone marrow aspirates, and acute promyelocytic leukemia was diagnosed. After CR was obtained with all-trans retinoic acid (ATRA) followed up with chemotherapy, the RT-PCR became negative. When he was readmitted in April, 1997, skin eruption on his chest and extremities were observed. Specimens taken for biopsy revealed leukemia cutis, and RT-PCR became positive in the same specimen. Bone marrow PT-PCR was also positive without abnormal promyelocytes. Although he was treated with oral ATRA 80 mg/day again, no significant improvement in leukemia cutis was noted. After combined therapy with Ara-C and acularubicin, skin eruption disappeared and bone marrow RT-PCR became negative. A second CR was then obtained. Although it is unknown whether the administration of ATRA is related to extramedullary relapse or not, we recommend combined chemotherapy for such cases.

Humans↗