Fulminant tumour lysis syndrome in acute myelogenous leukaemia with inv(16)(p13;q22)

Tumour lysis syndrome (TLS) is caused by rapid breakdown of malignant cells resulting in electrolyte disturbances and acute renal failure. TLS has rarely been described in patients with acute myelogenous leukaemia (AML). Between November 1997 and July 2001, 114 consecutive adult AML patients aged <60 yr received induction chemotherapy consisting of cytosine arabinoside 1.5 g m(-2) q 12 h x 12 doses and daunorubicin 45 mg m(-2) d(-1) x 3 doses. During induction chemotherapy (CT), seven patients (6.1%, 95% CI 2.5-12.2) developed fulminant TLS, resulting in acute renal failure; five of these seven patients had inversion of chromosome 16 [inv(16)(p13;q22)], and one patient had a biological equivalent [t(16,16)(p13;q22)]. Four of the TLS patients underwent leukapheresis for a presenting white blood cell (WBC) count > 100 x 10(9) L(-1) prior to commencing chemotherapy, and six patients subsequently required haemodialysis for a median of 2 (range 1-8) wk. One TLS patient died of intracerebral hemorrhage on day 10 and another patient of multiorgan failure on day 17. Of the other five patients, all entered a complete remission (CR) and recovered normal renal function. Four patients remain in continuous CR [median follow-up 20 (range 12-25) months]. One patient relapsed at 12 months and again developed TLS on re-induction. In univariate analysis, TLS patients were more likely to have an elevated presentation and pre-chemotherapy WBC counts, elevated serum creatinine, and uric acid levels at presentation, as well as an inv(16). In multivariate analysis, only serum creatinine and inv(16) remained statistically significant (P < 0.001 for each). Patients with an inv(16) are a unique AML subgroup at high risk for fulminant TLS.     

Secondary acute myeloblastic leukemia with t(16;21)(q24;q22) involving the AML1 gene

A t(16;21)(q24;q22) translocation was detected by fluorescence in situ hybridization in a patient with acute myeloblastic leukemia previously treated for malignant lymphoma. While the breakpoint on chromosome 21 was within the AML1 gene as determined by FISH, the gene partner on chromosome 16 could not be identified. Band 16q24 appears to be rearranged in several types of myeloid proliferation and a review of the literature shows that these rearrangements most often occur in secondary leukemia and myelodysplastic syndrome or are part of complex chromosomal rearrangements.     

A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1)

Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report here a 20-year-old woman with severe transfusion-dependent anemia and reticulocytopenia. White blood cells and platelet counts were normal. Bone marrow examination showed a low percentage of erythroid precursors (6%) and a marked dyserythropoiesis and dysmegakaryopoiesis. A diagnosis of MDS (refractory anemia according to the FAB classification) with erythroid hypoplasia was made. Cytogenetic analysis of the bone marrow and peripheral blood revealed a 46,XX,t(3;14)(p21.1;q24.1) translocation, which was confirmed by fluorescence in situ hybridization analysis. This translocation was detected in the apparently healthy younger brother, father, and aunt (father's sister) of the patient. Clonality of T cells in the patient was not confirmed by the polymerase chain reaction and heteroduplex temperature-gradient gel electrophoresis. IgM serology for B19 parvovirus was negative. Other conditions known to be associated with erythroid hypoplasia, such as thymoma, were not present. The patient failed to respond to immunosuppressive therapy (antithymocyte globulin and cyclosporin A). Administration of recombinant human erythropoietin improved her anemia. To our knowledge, this balanced translocation, namely t(3;14)(p21.1;q24.1), which is present both in the patient with MDS with erythroid hypoplasia and in the healthy members of the family, has not been defined previously.     

Acute myeloid leukaemia with t(9;11)(p22;q23) in a patient treated for adult T cell leukaemia

A 37-year-old male patient with adult T cell leukaemia (ATL) began receiving chemotherapy in March 1992. He achieved complete remission in May 1992, but developed acute myeloid leukaemia (AML, FAB subtype M2) with t(9;11)(p22;q23) in May 1993. The presence of chromosome 11 abnormality at band 11q23 in this patient suggests that the AML was related to the chemotherapy with etoposide for ATL. Furthermore, the combination of etoposide with two cytostatic drugs, cyclophosphamide and carboplatin, possibly induced the leukaemia early (14 months) after the start of chemotherapy. To our knowledge, this is the first report of therapy-related AML after chemotherapy for ATL.     

A novel translocation t(1;7)(p36;q34) in three patients with acute myeloid leukaemia

Studies of large numbers of patients have enabled the identification of relatively infrequent chromosome changes, such as inv(3)(q21;q26), t(6;9)(p23;q34) and t(8;16)(p11;p11), whose clinico-biological significance is gradually becoming clearer. Translocations involving chromosomes 1 and 7 are relatively rare in myeloid neoplasias, being found in far less than 1% of cases; the rearrangement that occurs most frequently consists of an unbalanced translocation [t(1;7)(p11; p11)], resulting in complete loss of 7q, associated with therapy-related or environmentally-induced high-risk myelodysplasia. We recently observed three cases of acute myeloid leukaemia (AML) with a previously unreported balanced translocation t(1;7) (p36;q34). Case 1 underwent autologous bone marrow transplantation and remains alive in CR; cases 2 and 3 relapsed after 10 and 4 months, respectively. The response to chemotherapy observed in our cases suggests that variable clinical features might be present in the broad cytogenetic category usually referred to as '7q abnormalities' and contributes to an interesting previous observation of prolonged disease-free survival in a subset of AMLs with 7q- as the isolated chromosome change.     

Der(16)t(l;16)(qll;qll) in myelodysplastic syndromes: a new non-random abnormality characterized by cytogenic and fluorescence in situ hybridization studies

The der(16)t(l;16)(qll;qll) is a frequent recurrent rearrangement in solid tumours such as breast carcinomas and Ewings sarcomas. Recently, this abnormality was described also in multiple myeloma. We identified a der(16)t(l;16)(qll;qll) in three patients with myelodysplastic syndrome, either during preleukaemic phase (n = 2) or at the time of blastic transformation (n = 1). Breakpoints were ascertained by fluorescence in situ hybridization (FISH) using specific centromeric a-satellite probes and whole chromosome painting for chromosome 1 and chromosome 16. These observations, combined with isolated cases of the literature, suggest that der(16)t(l;16)(qll; qll) is a non-random abnormality associated with myelodysplastic syndromes.     

Multiple myeloma and the translocation t(11;14)(q13;q32): a report on 13 cases

Complex cytogenetic abnormalities have been described in patients with multiple myeloma (MM). To better understand the significance of the most frequent translocation observed in MM, we studied the clinical characteristics of patients with MM and the t(11;14)(q13;q32) abnormality. A search of the cytogenetic database at the Mayo Clinic identified patients with MM and t(11;14)(q13;q32). The medical records were reviewed for the clinical characteristics of these patients. We identified 13 patients with MM and t(11;14)(q13;q32) determined by standard cytogenetic analysis; in 10 patients the abnormality was detected at the time of relapse (three with previously normal results of cytogenetic examination). At the time the translocation was detected, plasma cell (PC) leukaemia was clinically diagnosed in two patients. The median number of circulating PCs, as determined by the cytoplasmic immunofluorescence of T-cell-depleted peripheral blood mononuclear cells, was 1.1 × 10⁹/l (mean 1.74; range 0.0017–6.26 × 10⁹/l). On linear regression analysis there was a strong correlation between the number of circulating PCs and the number of bone marrow PCs. The median survival after demonstration of the translocation was 8.1 months. Of all patients, 10 died of disease progression and three were alive. Patients with MM who have t(11;14)(q13;q32) seem to have an aggressive clinical course, even when the abnormality is detected at the time of diagnosis, with evidence of many circulating PCs.     

Acute megakaryoblastic leukemia with translocation t(1;22)(p13;q13) in a 10-week-old infant.

A 10-week-old girl without Down syndrome developed an acute megakaryoblastic leukemia (AMKL). Bone marrow aspirates and biopsy showed megakaryoblastic infiltration with myelofibrosis. The diagnosis was made based on the findings that the positive reactions of leukemic cells to platelet peroxidase and to monoclonal antibodies which recognize platelet-specific surface glycoprotein (GP) IIb/IIIa and GP78. The blasts also showed myeloid and monocytoid differentiation antigens. The leukemic cells had a karyotype of 46,XX,t(1;22)(p13;q13). Our case and two other infantile cases reported by other investigators establish the novel association of the t(1;22) with AMKL.     

Severe aplastic anaemia in association with a unique constitutional translocation 46,XY,t(6;10)(q13;q22)c

Severe aplastic anaemia (SAA) is an uncommon disorder which may be associated with several congenital syndromes. However, it has rarely been described in association with a constitutional karyotypic abnormality. The breakpoint of the balanced t(6;10)(q13;q22) translocation described here does not disrupt any currently recognized gene of haemopoietic or stromal importance. This report also highlights the problems inherent in the use of bone marrow transplantation (BMT) for treating multiply transfused aplastic anaemia patients.     

Acute Myelomonocytic Leukemia with Dysplastic Bone Marrow Eosinophils Showing t(5;17)(q13;q11) and a Secondary Chromosomal Aberration, inv(16)(p13q22)

inv(16)(p13q22) is associated with de novo acute myelomonocytic leukemia with dysplastic bone marrow eosinophils (AMML Eo), which has a relatively favorable clinical course with a longer remission duration and better survival prospects. On the other hand, t(5; 17)(q13;q11), although relatively rare, has been reported to be a component of complex chromosomal abnormalities in myelodysplastic syndromes and secondary acute myeloid leukemia (AML). We treated a 29-year-old woman with the first reported case of de novo AMML Eo with inv(16)(p13q22) in addition to t(5; 17)(q13;q11). Although she attained complete remission (CR) immediately after induction therapy, the disease recurred 1 year after the completion of consolidation therapies. She underwent HLA-matched unrelated allogeneic bone marrow transplantation (UBMT), together with a myeloablative conditioning regimen, after achieving a second CR and has survived without a recurrence for more than 24 months since UBMT. In general, certain secondary chromosomal abnormalities are associated with the phenotype of the disease, which retains its essential biologic characteristics established by the primary abnormality. Accordingly, the primary nature of the leukemic cells in this case differs from the findings for core-binding factor AML with inv(16)(p13q22). We believe this report is the first of de novo AMML Eo with t(5; 17)(q13;q11) showing as a secondary chromosomal aberration with inv(16)(p13q22).