Secondary ANLL with t(11;19)(q23;p13) following etoposide and cisplatin for ovarian germ cell tumor.

This is a case report of a ten year old girl with ovarian germ cell tumor who was successfully treated with BEP chemotherapy. She developed acute myloid leukemia, AML-M5 with t(11;19)(q23;p13), 29 months after being off therapy. She received a cumulative dose of 2000 mg/m2 of etoposide and 400 mg/m2 of cisplatin. The association of etoposide and therapy related leukemia is reviewed.

Development of Ph positive chronic myeloid leukemia in a patient with chronic lymphocytic leukemia treated with total body irradiation: a rare association.

Philadelphia (ph) chromosome positive chronic myeloid leukemia developed in a patient treated for chronic lymphocytic leukemia after treatment with total body irradiation. The role of radiation in the development of CML is discussed.

Cytogenetic studies on patients of acute lymphoblastic leukemia Burkitt's type with (8;14) & (14;18) translocations.

Eight patients with acute lymphoblastic leukemia of Burkitt's type (ALL-L3) and two patients with Burkitt's lymphoma (BL) were subjected for cytogenetic studies. Translocation (8;14)(q24;q32) was present in nine (90%) patients; seven patients of ALL-L3 and two of BL. One ALL-L3 patient revealed t(14;18)(q32;q21) in 100 per cent metaphases. Additional clonal chromosomal anomalies present in these patients were deletion (6q) (40%) and trisomy 21(20%). The occurrence of t(8;14)(q24;q32) in ALL-L3 and BL patients in our series supports the association of t(8;14) with ALL-L3 and Burkitt's lymphoma.

Karyotypic findings as an independent prognostic marker in chronic myeloid leukaemia blast crisis.

Fifty-three patients with Ph positive chronic myeloid leukaemia in blastic phase were studied. Additional abnormalities were found in 29 (55%) patients and were more common in myeloid (64%) than lymphoid (45%) blast crisis. The most frequent were +Ph (32%), +8 (28%), +19 (19%), +20 (9%) and +21 (9%). i(17q) (9%) was associated with thrombocytopenia (5/5) and basophilia (2/5). The incidence of additional abnormalities was higher in patients treated with busulphan (70%) than hydroxyurea (44%). No significant differences were noted in the mean values of the clinical and haematological findings recorded at blast crisis between patients with only Ph positive (PP) cells and those with additional abnormalities (AP + AA). Univariate analysis identified karyotypic findings as an independent prognostic marker indicating its significance in assessing the response to therapy and survival after the onset of transformation.

Rhabdomyosarcoma. A cytogenetically interesting case report.

Chromosomal analysis was performed on the tumor tissue in a case of ocular rhabdomyosarcoma. Cytogenetic analysis revealed multiple clonal abnormalities. Derivative(5)t(1;5)(q21;q35) and t(2;11) (q21;q23) were present in all the metaphases analyzed (100%). Translocation(1;19)(q21;q13) was observed in 61% of the metaphases. Other clonal abnormalities present included +i(6p)(85%),i(17q)(38%),18q+(57%), 4p+ (38%), loss of the Y chromosome (33%), and presence of double minutes (12.8%).

Aniridia--Wilms' tumour association--a case with 11p 13-14.1 deletion and ventricular septal defect.

A two year old female child with bilateral wilms tumor (WT) along with multiple congenital anomalies like bilateral aniridia with congenital cataracts and nystagmus, microcephaly, mental retardation and ventricular septal defect has been described. The karyotype analysis revealed 46 xx, del 11p 13-14.1. Association of ventricular septal defect with the classical features of 'Aniridia-Wilms' tumor association' is an unusual feature in this case.

Childhood myelodysplastic syndromes: clinical features, cytogenetics and prognosis.

Sixteen children with myelodysplastic syndrome as defined by the French-American-British co-operative group are presented. The mean age was 10.5 (2.5 to 16) years, with a male predominance. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Seven patients presented with refractory anaemia with excess blasts, six had refractory anemia with excess blasts in transformation, and three had chronic myelomonocytic leukemia. Cytogenetic analysis done in 7 of the 16 patients, revealed karyotype abnormalities involving chromosomes 7, 8 and 17. One patient with Down's syndrome had karyotype of 47, XY, +21 (major clone) and 46, XY (minor clone). Five of these patients evolved to acute leukemia. The mean duration of survival was 5.5 months. Aggressive chemotherapy as a primary line of treatment induced remission in five out of six patients. Predominance of aggressive types of myelodysplastic syndromes in children and their good but short-lived response to aggressive chemotherapy suggests the need for early bone marrow transplantation following chemotherapy.

Fanconi's anemia: a clinico-hematological and cytogenetic study.

Eleven patients with typical features of Fanconi's anemia with cytogenetic studies were evaluated. Cytogenetic abnormalities was seen in all but one patient. Two patients had acute non-lymphoblastic leukemia (ANLL) and nine had Fanconi's anemia (FA). All patients with FA responded to oxymetholone and are well with a median follow up of 38.6 months. Both patients with ANLL died. This study stresses the need of an accurate cytogenetic analysis in FA patients along with a clinicohematological correlation.

Chromosomal characteristics of chronic and blastic phase of chronic myeloid leukemia. A study of 100 patients in India.

We report the cytogenetic findings of 100 patients with chronic myeloid leukemia (CML) [72 patients in chronic phase (CP) and 28 patients in blastic phase (BP)]. Of the 95 Ph + patients, six had Ph variant translocations involving chromosomes 1, 6, 7, 10, and 12. The percentage frequency of patients with chromosomal changes other than Ph was 7.3%. The additional aberrations (e.g., + Ph, + 8, i(17q), and + 19 were observed in 66.6% of BP patients. Of these anomalies, the frequency of + Ph and + 19 was higher in our patients than the incidence reported in literature. The association of + Ph and + 19 in patients with extramedullary T-cell blast crisis is an unusual finding as compared with reports in the literature and could be explained by geographic heterogeneity. The extra chromosomal abnormalities were almost absent in lymphoid blast crisis patients with blast phenotype of common acute lymphoblastic leukemia (ALL) type. Discrepancies were noted in different tissues (bone marrow and lymph node) in patients with extramedullary blast crisis of both myeloid and lymphoid type. These findings indicate the cytogenetic correlation with clinical and morphological picture, which consequently implicates the diagnostic and prognostic significance of chromosomal aspects.

T-lymphoid blast crisis in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is considered to be a pleuripotential stem cell disorder with the capacity to differentiate into myeloid, erythroid, megakaryocytic, and lymphoid cell lines. Consequently, blast crisis (BC) involving each of the above lineages has been well described. Among lymphoblastic crises, differentiation frequently occurs along B-cell lineage. We report four patients of CML who terminated in T-cell extramedullary BC in lymph nodes after a variable duration of chronic phase. The T-lineage was established by characteristic cytochemical staining and reactivity with a panel of anti-T-cell monoclonal antibodies. All four cases were Philadelphia (Ph) chromosome positive and demonstrated the Ph chromosome and associated anomalies (extra Ph, +19) in the lymph nodes. Our data adds to the growing evidence that CML is a disorder of the common stem cell from which T, B, and myeloid precursors originate.

Specific chromosomal changes in patients with acute nonlymphocytic leukemia from India.

We analysed forty consecutive patients with acute nonlymphocytic leukemia (ANLL) using methotrexate cell synchronization and 24 h-unstimulated cultures of bone marrow cells to determine the incidence of chromosomal aberrations and the association of specific anomalies with FAB morphological subtypes, in an Indian population. All patients demonstrated an abnormal karyotypic pattern. The specific chromosomal changes viz., t(9;22), t(8;21), t(15;17), t/del(11q), 12p- were found in M 1(3/5), M2(8/15), M3(8/8), M4(1/1) M5(2/4) and M2Ba(1/1) (M2 with Basophilia) patients. Abnormalities of 11q were also noted in two M2 patients showing monocytic involvement. A translocation involving chromosomes 6 and 9 was seen in one patient with M1 and two patients with M2. An inv(16) was observed in M1 (one case), M2 (two cases) and M6 (one case). A del(16) was noted in an M4 case. Although t(9;22) is frequently associated with M1 patients, it was also detected in M2 (two patients) and M4 (one patient). Among all the FAB specific anomalies described above, t(8;21) and t(15;17) were observed only in M2 and M3 patients, respectively. Interestingly, one M2 patient had two independent clones, one with t(8;21) and t(9;11). Deletion or translocation involving 11q was found in a Ph positive M4 patient. New structural rearrangements such as t(1;7) (q32;q36) in association with t(8;21), and t(14;22) (q32;q11) in association with del(11)(q23) were detected in a M2 and a M5 patient, respectively. In conclusion, our studies have revealed that the incidence of FAB specific abnormalities viz., t(8;21); t(15;17), t(9;22), t/del(11q) and also other recurrent anomalies viz., -7/7q-, +8 is much higher in our patients, as compared with other countries. This difference may be attributed to the influence of differential environmental exposure to unknown carcinogenic agents.

The occurrence of variant Ph translocations in chronic myeloid leukemia (CML): a report of six cases.

Variants of Philadelphia chromosome (Ph) translocation were detected in six of 95 Ph positive chronic myeloid leukemia (CML) patients (6.3 per cent). Two of these patients showed a Ph variant of 'simple' type, involving chromosomes 10 and 12. In four patients, the variant Ph was of 'complex' type involving a third chromosome:chromosomes 1, 6, 7 and 12 in addition to 9 and 22. Two of these resulted in the occurrence of a 'masked' Ph. In addition to variant Ph translocations, variant breakpoints such as q12 (two patients) and q13 (one patient) on chromosome 22 were observed in another three patients with t(9;22).

Cytogenetic findings in patients with acute promyelocytic leukemia and a case of CML blast crisis with promyelocytic proliferation.

Nineteen patients with acute promyelocytic leukemia (APL) and one with promyelocytic blast crisis were studied by a methotrexate cell synchronization technique and by 24-hour short-term culture. Nineteen cases of APL included two cases of the microgranular variant (M3V). Except in one case of M3V, t(15;17) was detected in all patients. The breakpoints were determined as 15q22 and 17q12-21. A chronic myeloid leukemia (CML) blast crisis patient with high promyelocyte count also had a t(15;17) as well as a masked Ph chromosome. Other abnormalities, such as +8,del(7q) and an i(17q), were also observed in some patients. Our studies have indicated that 1) the translocation (15;17), characteristic of APL, was present in our population in almost all patients; 2) the presence of an identical abnormality in a promyelocytic CML blast crisis supported and confirmed the phenomenon of association of specific chromosome change with target cell type; and 3) the precise localization of breakpoints on chromosome 17 is still difficult to determine. The identification of as yet unknown genes at region 17q11-q21 and their subsequent translocation on chromosome 15 will help in assigning a precise position to these breakpoints.

Cytogenetic features of erythroleukemia (EL). A study of 11 cases.

Cytogenetic studies were carried on 11 patients with erythroleukemia (EL). Most of these patients showed major chromosomal abnormalities (MAKA), karyotypic instability, and complex chromosomal rearrangements. On the basis of the cytogenetic criteria, 10 patients could be distinguished into erythroid (9 cases) and myeloid types of EL (1 case). The patients did not show any consistent chromosomal abnormality. However, abnormalities of chromosomes 1, 3, 7, 8, 16, and 17 were seen in more than one patient. In patients with the erythroid type of EL, besides the MAKA pattern, three patients showed increased frequency of hyperdiploid polyploid cells ranging from triploidy to tetraploidy.

Cytogenetic studies in Hodgkin's disease.

Chromosome studies were carried out by G-banding technique on the bone marrow cells of 24 newly diagnosed, untreated Hodgkin's disease patients and 25 treated patients. Seven of these treated patients had also been studied at diagnosis. In the untreated group of patients, cytogenetic studies were carried out on stimulated peripheral blood lymphocytes in 11 patients and on skin fibroblasts in five. Of the 24 untreated patients, 14 showed normal diploid pattern, while 10 were seen with 8-30 per cent chromosomally aberrant cells in the bone marrow. The frequent anomalies were trisomy C/8 and trisomy 22 seen in 5 and 4 patients respectively. The cytogenetic picture of peripheral blood lymphocytes revealed normal diploid pattern in 7 patients; while 4 other patients showed abnormal clones with trisomy 21. The cultured skin fibroblasts represented normal diploid karyotypes. An altered karyotypic pattern was seen in the bone marrow of treated patients. In patients with abnormal karyotypes, the common anomalies were monosomy C, monosomy D/15 and trisomy 21. In patients which showed no involvement of the bone marrow by haematological parameters, chromosomally abnormal karyotypes were seen in the marrow. Thus, marrow involvement can be detected earlier cytogenetically.

Studies on sister chromatid exchanges in patients with Hodgkin's disease.

Sister chromatid exchange frequencies were analyzed in bone marrow cells and in stimulated peripheral blood lymphocytes from 20 patients with Hodgkin's disease. Sister chromatid exchange studies were also carried out in the bone marrow of eight and peripheral blood of 11 normal subjects separately. Among the patients, ten were newly diagnosed and ten patients were survivors who had received therapy 30-64 months prior to studies. The mean sister chromatid exchange frequencies in bone marrow and peripheral blood of untreated patients were 3.93 +/- 0.7/cell and 4.09 +/- 0.91/cell, respectively, which were not significantly different from those of normal subjects (3.22 +/- 0.7/cell and 5.16 +/- 1.3/cell in bone marrow and peripheral blood, respectively). The mean sister chromatid exchange frequencies in bone marrow and peripheral blood in five of the untreated patients 3-4 months after initial therapy and in a treated (30-64 months after therapy) group were close to the sister chromatid exchange values of the untreated group. Analysis of the distribution of exchanges per chromosome or chromosome groups showed a nonrandom distribution of exchanges in chromosomes #1, #2, and #3, and in E-, F-, and G-group chromosomes in the normal controls and in Hodgkin's disease patients.