c-myc amplification is usually associated with lymphoid malignancies and Burkitt's lymphoma in particular. We present a case of AML with c-myc amplification which was associated with homogenous staining regions (hsr) and double minutes (dmin). The administration of GCSF following induction chemotherapy resulted in a marked increase in blast numbers. The GCSF was stopped and further courses of chemotherapy given, which resulted in complete remission. The patient relapsed 7 months after diagnosis and failed to go into a second remission with reinduction therapy. We conclude that c-myc amplification is a rare event in AML, but may be associated with chemotherapy resistance and a poor prognosis, are as dmins and hsr. Growth factors should be used with caution in these patients.
Using centromere-specific probes and a fluorescence in-situ hybridization (FISH) technique in cases of childhood hyperdiploid acute lymphoblastic leukaemia (ALL), cells with extra copies of chromosomes can be differentiated from normal cells by their extra signals in both metaphase and interphase nuclei. In this way the entire cell population, not only those cells in division, can be analysed, thereby providing a valuable technique not only for determining leukaemia cell karyotype at diagnosis but also for the detection of minimal residual disease (MRD). We have conducted 161 analyses of remission bone marrow aspirates (BMs) in 13 children with hyperdiploid ALL. Slides were analysed blind and in parallel to 35 control samples. Control BMs showed very low numbers of trisomic cells (mean +/- 2 x SD = 0.13 +/- 0.34%). MRD was detected in 5/13 cases of ALL investigated while on chemotherapy. One out of five newly diagnosed cases and all three relapse cases of ALL had significantly raised levels of hyperdiploid cells in day 28 BMs. The presence of detectable disease in day 28 BMs suggests the need for larger studies to find whether this data is of prognostic value.
Aims-To investigate proliferative activity in leukaemic and lymphomatous bone marrow infiltrates and to assess the feasibility of transport of specimens among institutions.Methods-Proliferative activity in bone marrow trephine cryosections from 99 patients with non-Hodgkin's lymphoma (NHL), 23 patients with acute myeloid leukaemia (AML), 11 with acute lymphoblastic leukaemia (ALL), and two with acute undifferentiated leukaemia (AUL) was investigated. Infiltration was seen in 52 out of 99 cases of NHL on bone marrow cryosections. A score was devised to assess pathological infiltrates in bone marrow trephine cryosections using the monoclonal antibody Ki-67. This method of scoring gave a measure of non-erythroid proliferative activity. Results-Mean Ki-67 positivity in bone marrow infiltrates in 31 low grade B cell lymphomas (Kiel classification) was 0*3% before and 4-7% after treatment, 16'4% in seven high grade B cell lymphomas, and 17-8% in 12 peripheral T cell lymphomas. In 48 cases of NHL, bone marrow cryosections had not been infiltrated, and in all but one case the percentage of Ki-67 positive cells in normal marrow was less than 3%; the remaining case showed coexistent myelodysplasia and 8% bone marrow Ki-67 positivity. In eight cases of common ALL at diagnosis, the mean Ki-67 positivity in marrow cryosections was 24-9%, significantly higher than the 2-4% Ki-67 positivity seen in AML (p < 0.05).One of the two cases of common ALL with less than 1% Ki-67 positivity was refractory to treatment. Conclusions-Proliferative activity of erythroid elements in the bone marrow varies greatly. Immunostaining of bone marrow cryosections using permits accurate assessment of non-erythroid proliferative activity in lymphomas and leukaemia. High grade B cell lymphomas and peripheral T cell lymphomas invading the marrow have very similar mean proliferative activities. Such levels of proliferation are of the same order as those seen in common ALL, but much higher than those seen in AML. (7 Clin Pathol 1994;47:209-213) Proliferative activity in marrow can predict remission and length of remission in acute leukaemia, yet no data on the proliferation rate in trephine biopsy specimens are being collected on patients entering current trials.'2 Proliferation in lymph nodes also seems to be of prognostic value in non-Hodgkin's lymphoma (NHL).3 Many techniques for assessing proliferation exist: these include tritiated thymidine autoradiography, flow cytofluorimetry to determine the 2n-4n cell percentage, and bromodeoxyuridine (BrdU) preincubation with anti-BrdU staining and transferrin receptor analysis. Tritiated thymidine use involves lengthy cell incubation and the use of radioisotopes; the BrdU method also involves incubation of cell suspensions and, like thymidine methods, may overestimate proliferating cells caused by non-S phase DNA synthesis and repair.4Ki-67 is a monoclonal antibody which labels a proliferation associated antigen present in the nuclei of stimulated peripheral blood lymphocytes in S, G, M, and late...
SUMMARY Bone marrow infiltrates taken from 11 patients with peripheral T cell lymphoma were immunophenotyped as T cell lymphoma using monoclonal antibodies on frozen bone marrow trephine biopsy specimens. In nine these were taken at diagnosis and in two after failure of treatment to eradicate lymphoma in the marrow. Patterns of infiltration were as follows: diffuse (n = 4), interstitial (n = 1), nodular (n = 1), focal (n = 5). All cases were CD3 positive and 10 were CD2 positive; five lacked expression ofeither CD5 or CD7, or both markers. In nine the determination ofT cell phenotype depended on analysis of the frozen bone marrow trephine biopsy specimen as there was no other biopsy tissue available for study. In the other two cases there was agreement between the immunophenotypes seen in lymph node and bone marrow infiltrates.
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