Search PubMed⌕ Search

Biomedical subjects

P Philip

Publications and source records attributed to P Philip.

At least 91 records · Page 5Linked to original sources

Chromosome characteristics of therapy-related acute non-lymphocytic leukemia and preleukemia: possible implications for pathogenesis of the disease.

Most cases of therapy-related acute nonlymphocytic leukemia or preleukemia show chromosome aberrations, primarily loss of whole chromosomes No. 5 and/or No. 7 or the long arms of these two chromosomes. Other abnormalities involve chromosome No. 21, often rearranged at band 21q22, and chromosome No. 17, in some cases rearranged at band 17p13. Important cellular genes have recently been localized to these regions, including the gene for one hematopoietic growth factor and the gene for the receptor for another hematopoietic growth factor. It is suggested that the total loss or change of structure or expression of some of these genes resulting from the various chromosome aberrations may be of pathogenetic significance in therapy-related acute nonlymphocytic leukemia.

Antineoplastic Agents↗

Translocations and deletions with breakpoint on 21q are nonrandomly associated with treatment-related acute nonlymphocytic leukemia and preleukemia.

Six of 70 (8.6%) consecutive cases with therapy-related acute nonlymphocytic leukemia (ANLL) or preleukemia had a translocation or deletion with a breakpoint on 21q. Such aberrations were seen in only one of 200 (0.5%) consecutive cases of de novo ANLL examined at our laboratory. The figures reflect a 17.1-fold increased incidence of 21q aberrations in therapy-related ANLL or preleukemia, compared with ANLL de novo. The difference is highly significant (p = 0.003). The increased incidence of 21q aberrations in therapy-related myelodysplastic syndromes was confirmed by literature studies. Band 21q22 was most often involved. Cases with t(8;21), which is strongly associated with the M2 variant of ANLL, or cases with i(21q), which is supposedly due to a centromeric misdivision, were not included in the count. It is concluded that the 21q aberrations are associated with treatment-related ANLL or preleukemia with at least the same degree of specificity as aberrations of #5 and #7.

Acute Disease↗

Acute promyelocytic leukemia with t(15;17) and t(2;17;15).

Cytogenetic examination in a case of acute promyelocytic leukemia (FAB-M3) demonstrated a stem line with t(15;17) and a side line with t(2;17;15). This observation indicates either clonal evolution from the standard translocation or a de novo complicated translocation. Previous cases with three-way translocations in acute promyelocytic leukemia have been reviewed. Three-way translocations seem to occur with similar frequency in M2 and M3 types of acute myeloid leukemia and in chronic myelocytic leukemia.

Child↗

Cytogenetic characteristics of therapy-related acute nonlymphocytic leukaemia, preleukaemia and acute myeloproliferative syndrome: correlation with clinical data for 61 consecutive cases.

Cytogenetic studies were performed on a new series of 23 patients with therapy-related acute non-lymphocytic leukaemia, preleukaemia or an acute myeloproliferative syndrome. In our total series of now 61 cases studied by chromosome banding techniques, at least one of the abnormalities -7, 5q-, 7q- or -5 or some related unbalanced translocations, primarily -7, +t(1q7p), was observed in 40 patients. The critical region for the deletions of chromosome no. 5 comprises bands 5q22 to 5q33 and of chromosome no. 7 bands distal to 7q22. The third most frequently involved chromosome was no. 21, rearranged at band 21q22 in the three patients with 21q+ and in one patient with 21q-. An i(21q) was observed in two patients, a -21 in four patients and a -22, +t(21q22q) and a -5, -21, +t(5p21q) in one patient each. Other characteristic abnormalities included total loss or rearrangements of the short arm of chromosome no. 17, observed in nine patients. One patient had a -12, three others had rearrangements resulting in a partial or total loss of the short arm of chromosome no. 12. A 19q+ with translocation to band 19q13 was observed in three cases, a -18 in three cases and a 3p- in four cases. Thirty-one patients with multiple chromosome aberrations experienced a significantly shorter survival as compared to 13 patients with a normal karyotype (P = 0.02) and 17 patients with one single chromosome aberration (P less than 0.01).

Acute Disease↗

Simultaneous presence of translocations t(14;18) and t(2;8) in a case of chronic lymphocytic leukemia.

We report a patient with classical chronic lymphocytic leukemia of IgM kappa phenotype and a stable clinical course, in which repeated chromosome analyses of blood lymphocytes revealed the coexistence of t(14;18), a marker often associated with follicular low grade lymphocytic lymphomas, and t(2;8), a variant of the t(8;14) typically seen in Burkitt's lymphoma. Both these translocations involve immunoglobulin gene regions, the t(2;8) being almost always found in patients with kappa light chain restriction. However, in an EBV-immortalized cell line of this patient, most karyotypes contained t(14;18) alone, without the t(2;8). This suggests that t(14;18) was the primary cytogenetic event, and that t(2;8) evolved subsequently. As a secondary cytogenetic event, the t(2;8) may not share the grave clinical consequences of a primary t(2;8) as seen in Burkitt's lymphoma and related disorders.

Aged↗

[Gangrenous streptococcal cellulitis of the hand].

The authors report three cases of streptococcal cellulitis of the hand with gangrene. The severity of this disease is underlined. Occasionally, segmentary amputation may be necessary. Onset of gangrene may be explained by a double mechanism : streptococcal infection may induce vasculitis obliterans of the regional vessels, extensive edema with ecchymosis may be a factor of segmental compression. Treatment should include excision of the entrance door, antibiotherapy and fasciotomy as needed.

Adult↗

Acute nonlymphocytic leukemia following treatment of testicular cancer and gastric cancer with combination chemotherapy not including alkylating agents: report of two cases.

Acute nonlymphocytic leukemia following combination chemotherapy not including alkylating agents or radiotherapy was observed in one patient treated for testicular cancer and in another treated for gastric cancer. Both patients presented clinical, cytologic, and cytogenetic findings uncharacteristic for secondary acute nonlymphocytic leukemia. It is discussed whether these two cases of leukemia indicate a risk of secondary leukemia following chemotherapy with cisplatinum and adriamycin.

Acute Disease↗

Development of acute nonlymphocytic leukaemia (ANLL) in myelomatosis.

On the basis of the literature, so-called secondary acute nonlymphocytic leukaemia (S-ANLL) in myelomatosis is reviewed. Using the banding technique, cytogenetic changes including hypodiploidy and partially or totally missing chromosomes # 5 and # 7 are recorded. The findings are in accordance with the cytogenetic changes seen in S-ANLL in other malignancies which have been treated with cytostatics, especially alkylating agents. So, S-ANLL in myelomatosis seems to be a result of treatment with cytostatics, though a causal relationship has to be documented.

Acute Disease↗

Predictive value of bone marrow cultures in 48 patients with acute myeloblastic leukaemia or myelodysplasia both secondary to treatment of other malignant diseases.

The growth pattern of bone marrow cells in agar cultures was studied in 48 patients with acute myeloblastic leukaemia or myelodysplasia, secondary to cytoreductive treatment, and compared to other laboratory findings. At diagnosis the status of the patients was: acute myeloblastic leukaemia (AML) in 9, acute myeloproliferative syndrome (AMS) in 13 and preleukaemic syndrome (PL) in 26 patients. 20 of the 39 patients with AMS and PL developed acute leukaemia, 15 of them within 1 year. 15 died of complications to cytopenia and only 4 are still alive and without leukaemia, observed from 8 to 55 months. Progression to AML was predicted from the agar cultures by increased cluster growth. Among 18 patients with increased cluster growth at diagnosis 14 subsequently developed AML. Among 21 patients with normal or decreased cluster growth at diagnosis 6 patients developed AML, but after conversion of the growth pattern to increased cluster growth. In 2 patients the increased cluster growth disappeared spontaneously and the patients are long-term leukaemia-free survivors. Colony growth pattern, conversely, was not related to leukaemic progression. Only 1 patient had normal growth pattern at diagnosis with respect to both clusters and colonies. Survival was short, with a median of about 7 months, unrelated to growth pattern and leukaemic progression.

Adult↗

Risk of acute nonlymphocytic leukemia and preleukemia in patients treated with cyclophosphamide for non-Hodgkin's lymphomas. Comparison with results obtained in patients treated for Hodgkin's disease and ovarian carcinoma with other alkylating agents.

Of 602 patients treated for non-Hodgkin's lymphomas, 9 developed overt acute nonlymphocytic leukemia or preleukemia with refractory cytopenia and cytogenetic abnormalities of the bone marrow. A Kaplan-Meier estimate of the cumulative probability of leukemic complications was 6.3 +/- 2.6% (mean +/- SE) 7 years after start of treatment. All 9 patients with leukemic complications belong to a major subgroup of 498 patients treated with alkylating agents, predominantly cyclophosphamide. The risk of leukemic complications in this subgroup was compared with the risk in 312 patients treated with other alkylating agents for Hodgkin's disease, and with the risk in 553 patients treated with dihydroxybusulfan for ovarian carcinoma. Cumulative 9-year risks were 8.0 +/- 3.3%, 12.8 +/- 3.5%, and 7.1 +/- 1.9%, respectively. The general risk of secondary leukemia after long-term treatment with alkylating agents ranges from 1% to 1.5% per year from 2 to at least 9 years after start of treatment.

Acute Disease↗

Acute nonlymphocytic leukemia, preleukemia, and solid tumors following intensive chemotherapy of small cell carcinoma of the lung.

Six of 796 patients treated with intensive combination chemotherapy for small cell carcinoma of the lung developed overt acute nonlymphocytic leukemia (ANLL) (three patients) or preleukemia with severe refractory cytopenia and clonal cytogenetic abnormalities in bone marrow cells (three patients). The latent period to development of preleukemia or leukemia was less than two years in four of the six patients. The cumulative risk of preleukemia and leukemia according to a Kaplan-Meier estimate was 14.0% +/- 6.9% (mean +/- SE) four years after the start of treatment. The relative risk of overt ANLL was 77, since three cases were observed v 0.039 cases expected, based on the age- and sex-specific incidence of acute nonlymphocytic leukemia in the general Danish population. The risk of secondary solid tumors was not increased. The possible causes of the exceptionally early appearance and very high cumulative risk of leukemic complications found in the present study, as compared to previous experience in other malignant diseases, is discussed, including the implications for future therapy of patients with small cell lung cancer.

Acute Disease↗

Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. II. Bone marrow cytology, cytogenetics, results of HLA typing, response to antileukemic chemotherapy, and survival in a total series of 55 patients.

Secondary acute nonlymphocytic leukemia or its earlier stages, preleukemia or an acute myeloproliferative syndrome with refractory cytopenia and clonal cytogenetic abnormalities of the bone marrow, was diagnosed in 55 patients previously treated for other malignant diseases. In patients with overt leukemia, cytologic, and cytochemical studies showed predominance of the French-American-British (FAB) type M2. Cytogenetic examination demonstrated a normal karyotype in 11 cases, whereas clonal abnormalities were observed in 44 patients. Defects of chromosome 7 were observed in 24 cases, most often -7, and defects of chromosome 5 in 14 cases, most often 5q-. In addition, chromosomes 3 and 17 were possibly nonrandomly involved. Other abnormalities commonly observed in de novo acute nonlymphocytic leukemia as t(8;21) and t(15;17) were not observed and +8 rarely seen in secondary leukemia. The survival from the leukemic complication was short for the whole group of 55 patients (median, 7 months). However, a significantly longer survival was observed in a subgroup of 11 patients with a normal karyotype (P less than 0.01), due to a favorable response to antileukemic chemotherapy, and in a subgroup of 11 patients with -7 or -C as the only cytogenetic abnormality (P less than 0.01), due to a prolonged preleukemic phase, compared with the remaining 33 cases with mostly multiple karyotypic abnormalities. Three preleukemic patients with -7 who were studied during transformation to overt leukemia all developed additional cytogenetic abnormalities. According to the two-step or multistep hypothesis for malignant transformation, the prolonged preleukemic course in patients with -7 as the only abnormality could represent a premalignant stage, in which further evolution is required for development of overt leukemia. The patients showed a random distribution of blood groups and HLA types.

Acute Disease↗