Acute lymphoblastic leukemia with a late- appearing Philadelphia chromosome: case report and review of the literature.

UNLABELLED: We describe a rare presentation of acute lymphoblastic leukemia in a young adult male who at the beginning of the disease lacked the Philadelphia chromosome in bone marrow and blood cells and fluorescence in situ hybridization was negative for the presence of a clone with the BCR-ABL1 rearrangement. The patient initially had pancytopenia with a blast cell count of 5% in the peripheral blood that evolved to a phase with progressive leukocytosis and a sudden rise in blast cells 7 months later. At this time, his bone marrow aspirate showed the presence of a neartriploid karyotype containing two Philadelphia chromosomes. The multiple karyotypic changes observed in our patient support the notion that leukemic progression involves several cytogenetic evolutionary processes, the first step of which may not necessarily involve acquisition of the Philadelphia chromosome. KEYWORDS: Late-appearing Philadelphia chromosome, adolescent ALL, BCR-ABL1, dasarinib.

Secondary acute myeloid leukemia after successful treatment for osteosarcoma.

Secondary acute myeloid leukemia (sAML) is a rare complication following chemotherapy for osteogenic sarcoma. However, the exact offending drug is difficult to prove as there is no consistent data. It usually develops 2 years after completion of therapy. We report a case of sAML that developed within 8 months of completing the treatment. The patient was treated with cisplatin, doxorubicin and high-dose methotreaxate followed by surgery (amputation). Eight months after completion of therapy, while on follow-up, he presented with leukocytosis and thrombocytopenia and confirmed to have AML.

A novel variant translocation t(6;8;21)(p22;q22;q22) leading to AML/ETO fusion in acute myeloid leukemia.

Acute myeloid leukemia associated with translocation t(8;21) and the underlying AML1-ETO gene fusion is considered as a distinct type of leukemia with characteristic morphologic features. Variant and masked forms of the classic translocation t(8;21) are uncommon and their clinicopathologic features are less well characterized. We report here a patient with a masked translocation involving chromosomes 6,8 and 21. Chromosomal study at diagnosis initially reported the karyotype as translocation between chromosomes 6 and 8 without visible involvement of chromosome 21. However, fluorescence in situ hybridization studies revealed the involvement of chromosome 21 in the translocation and presence of the AML1-ETO chimeric gene. The complex rearrangement t(6;8;21) observed in our patient was not previously described and could be not detected without combination of techniques. Our case illustrates the challenge of recognizing complex aberrations that occur with variant t(8;21) and further reinforces the utility of fluorescence in situ hybridization applications in more accurate characterization of chromosome abnormalities which can lead to more precise therapeutic stratification.

Primary treatment of acute myeloid leukemia (non M3) in elderly: a review.

Treatment of acute myeloid leukemia (AML) in the elderly has always been a challenging task. Acute myeloid leukemia in older adults is a biologically and clinically distinct entity. Based on analysis of cytogenetic and molecular data, it is known that leukemic cells in older patients are intrinsically resistant to standard chemotherapy. Due to comorbid disease and impaired bone marrow stem cell reserve, older adults tolerate myelosuppressive chemotherapy poorly, with a treatment-related mortality rate of 25%. In spite of various available targeted therapies, the overall survival has not improved dramatically in the past decade. The ideal post remission regimen in this population has always been a matter of debate. Standard allogeneic bone marrow transplantation is too dangerous to be considered as a mean to eradicate minimal residual disease after remission is obtained and myelointensive chemotherapy is not a beneficial post-remission strategy in this age cohort. These disappointing results call for more effective and less toxic therapeutic options. The advent of non-myeloablative regimens has shown some prospects in select group of patients with good performance status. This review focuses on current therapeutic options available in this group of patients.

Acute myeloid leukemia as a genetic disease. Review article.

The number of recurring genetic abnormalities recognized in acute myeloid leukemia (AML) has increased rapidly in recent years and at present, acute leukemia is probably the most extensively analyzed human cancer. Combined cytogenetic and molecular genetic studies have revealed that clonal chromosome abnormalities are present in the majority of patients with AML that are very closely, and sometimes uniquely, associated with distinct subsets of leukemia. Detailed analysis of these rearrangements indicates that in most instances chromosome rearrangements result in gene fusions leading to chimeric abnormal protein with oncogenic potential. Continued identification and characterization of genes involved in the development of leukemia has a major impact on our understanding of the molecular biology of cancer and in formulating of biologically based therapies.

All-transretinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia.

BACKGROUND: All-transretinoic acid (ATRA) and chemotherapy has improved complete remission rates and disease free survival in acute promyelocytic leukemia (APL). There is scanty data from Middle East. AIM: To determine the efficacy of ATRA and multi-agent combination chemotherapy in treatment of APL in a single Centre in Kuwait. SET-UPS AND DESIGN: Tertiary cancer centre, retrospective study. METHODS AND MATERIAL: All newly diagnosed APL patients were treated with oral ATRA 45 mg/m2 daily until complete remission (CR), intravenous daunorubicin 50 mg/m2 on days 1,3 and 5, cytosine arabinoside 100 mg/m2 12 hrly on days 1 through 10 and etoposide 100 mg/m2 on days 1 through 5. Post remission three courses of intensive consolidation chemotherapy were administered. Since October 1999, maintenance chemotherapy consisting of oral 6 mercaptopurine 9 mg/m2 daily, methotrexate 15 mg/m2 weekly and ATRA 45 mg/m2 for 2 weeks every three months was added. Complete remission rates and duration, relapse rate and toxicity were studied. RESULTS: 22 of 24 evaluable patients (91.6%) achieved CR. The median duration of remission was 13 months (range 2-55 months). Three patients (12.5%) relapsed. Two patients (8.3%) developed retinoic acid syndrome and responded to dexamethasone. Five patients (20.8%) died one each of refractory disease, during remission induction and of relapse. Two patients died while in remission. CONCLUSION: ATRA and combination chemotherapy results in high complete remission rates and low relapse rate in newly diagnosed APL. Maintenance therapy may be useful in preventing relapses.

Chromosome aberrations in de novo acute myeloid leukemia patients in Kuwait.

Cytogenetic analysis was successfully performed at the time of diagnosis in 45 patients with de novo acute myeloid leukemia, including 10 children and 35 adults. In approximately 73% of AML patients (35 patients) clonal chromosome abnormalities were detected at the time of diagnosis. Twelve patients (22.8%) had apparently normal karyotypes. Recurring aberrations found in 22 of patients with abnormal karyotypes included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), trisomy 8, monosomy 7 and del(5q). The highest frequency of chromosome changes was observed in AML-M3. The occurrence of the classical cytogenetic abnormalities was not a ubiquitous phenomenon. In 11 patients previously not described miscellaneous clonal chromosomal abnormalities were detected. Clonal chromosomal abnormalities detected in AML have shown correlations between specific recurrent chromosomal abnormalities and clinico-biological characteristics of the patients, therefore have been repeatedly shown to constitute markers of diagnostic and prognostic significance. Moreover, ongoing cytogenetic analysis can identify new nonrandom chromosome aberrations in AML and contribute to the identification of novel genes involved in the development of cancer, which can lead to better understanding of the disease pathogenesis.

Sequential standard dose mitoxantrone and cytosine arabinoside for newly diagnosed adult acute myeloblastic leukemia.

Twenty one adult patients with previously untreated acute myeloblastic leukemia (AML) were treated with sequential mitoxantrone and standard dose cytosine arabinoside remission induction therapy. The median age was 33 years (range 17-56 years). Complete remission (CR) was achieved in 80% (17/21 cases) and 76% (16/21 cases) achieved CR after one course of induction therapy. The median duration of disease free survival was 9 months with an actuarial disease free survival of 22% at 43 months. The non-hematological toxicity was acceptable. We conclude that sequential mitoxantrone and cytosine arabinoside combination therapy is an effective antileukemic regimen which produces high CR rates in previously untreated adult patients with AML.

Recent trends in the incidence of lymphomas in Kuwait.

All cases of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) reported to the Kuwait Cancer Registry between 1980-1989 were analyzed. Age specific and age standardized incidence rates were calculated for Kuwaiti and non-Kuwaiti males and females for the two periods of 1980-1984 and 1985-1989, and compared to detect short term changes. The study of 153 cases of HD and 325 cases of NHL in 1980-1984 and 213 cases of HD and 338 cases of NHL in 1985-1989 showed that HD incidence was stable in the two periods, the mixed cellularity subtype frequency and incidence declined, while the frequency and the incidence of nodular sclerosis increased significantly in the second period. These changes were most significant in the non-Kuwaiti males. The NHL incidence declined significantly in the 1985-1989 period. The incidence of low grade and intermediate grade NHL declined in the period of 1985-1989. The high grade NHL frequency increased, however, the annual incidence rate increase was not significant. The change in the HD subtypes may probably be related to the improvement in the socio-economic condition. The higher proportion of high grade lymphomas may be related to the population structure in Kuwait and is not related to the acquired immunodeficiency syndrome.

Bilateral osteonecrosis of the head of the femur complicating acute promyelocytic leukemia: a sequel to treatment of retinoic acid syndrome with dexamethasone.

The complication of 'retinoic acid syndrome' occurs in 25-30% of patients with acute promyelocytic leukemia (APL) treated with all-transretinoic acid (ATRA). Early dexamethasone therapy has reduced mortality from this complication. No long-term sequel of the syndrome or its treatment with dexamethasone has been described. We report a patient with APL treated with ATRA who developed avascular necrosis of both femoral heads following treatment of retinoic acid syndrome with short-duration, high-dose dexamethasone.

Febrile neutropenia in cancer patients in Kuwait: microbial spectrum and outcome.

A sample of 100 consecutive febrile neutropenic episodes in cancer patients in Kuwait was studied. Acute leukaemias (44%) and lymphomas (29%) were the most frequent underlying cancers; 21 bacteraemis (gram-positive 10, gram-negative 9, polymicrobial 2) were encountered. Staphylococcous epidermidis and Escherichia coli were the commonest organisms. Urinary tract infection occurred in 30% of the microbiologically documented cases. A total of 84 episodes responded to therapy and 9 of the 14 deaths were secondary to infection.

The epidemiology of leukemia in Kuwait.

This study reports the occurrence of leukemia subtypes in Kuwait between 1979 and 1989. The cases were analyzed by age, sex, Kuwaiti and non-Kuwaiti nationality status. Of the total 723 cases, acute lymphoblastic leukemia (ALL) was the most frequent (44.2%), exhibited a peak incidence in the 0-4 years age group and was also the most common leukemia of childhood (90.5%). Acute myeloblastic leukemia (AML) constituted 32.4% of leukemia and showed a progressive increase in incidence with age. Chronic myeloid leukemia (CML) constituted 14.8% and chronic lymphocytic leukemia (CLL) 8.6% of all cases. The incidence, age and sex distribution of ALL, AML and CML was similar to that in the developed Western countries while the lesser frequency of CLL was similar to that in the Orient. This pattern of leukemia subtypes may be related to the population structure consisting of the predominantly young in Kuwait, and the peak incidence of ALL in the very young to the socio-economic conditions.

Human immunodeficiency virus (HIV) infection associated with acute myeloblastic leukemia in a low HIV prevalence area.

PIP: The association of acute myeloblastic leukemia (AML) and HIV infection is rare. Only eight cases had been reported of coexistence until 1990, and the association may be due to chance. HIV infection is associated with T cell immunodeficiency, however, and may contribute to the development of AML in such patients either due to defective T cell regulation of hemopoiesis and/or due to failure of immune surveillance. Previous reports have been from relatively high HIV prevalence areas. The authors report two cases of coexistent HIV infection and AML from a low HIV prevalence area found in routine screening for HIV. An 18-year-old male presented December 1991 with fever and fatigue, and a 70-year-old male presented February 1993 with cough and expectoration. Experience is limited in managing AML with coexistent HIV infection. Complete remissions have, however, been documented after low-dose cytosine arabinoside and intensive combination chemotherapy. The younger of the two patients received chemotherapy and tolerated it like HIV-negative AML patients, but succumbed to possible fungal pneumonia and intracerebral infection while in remission. The authors stress in closing that coexistent HIV infection in patients with AML may be overlooked especially in low HIV prevalence areas. Routine HIV screening of AML patients should be considered.^ieng

Trisomy 4 and de novo acute myelomonocytic leukemia in a Kuwaiti patient.

Trisomy 4 is a rare but specific karyotypic abnormality associated with primary and secondary acute myeloblastic leukemia (AML). We report such an occurrence in a Kuwaiti patient with de novo acute myelomonocytic leukemia and its disappearance on achievement of complete remission.