Novel constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) in patients with acute leukemia

Certain constitutional translocations have been described to be associated with an increased risk of malignant diseases. We report here two patients, one with acute myeloid leukemia (AML) and another with biphenotypic acute leukemia, in whom constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) were observed, respectively. To our knowledge, none of the above translocations has been previously reported.     

Secondary acute lymphoblastic leukemia with t (4; 11): Report on two cases and review of the literature

Summary We report two cases of secondary acute lymphoblastic leukemia (ALL) with t (4;11) (q21;q23) translocation occurring after chemotherapy and radiotherapy for a prior cancer. Seven previously published cases of secondary ALL with t (4; 11) (q21; q23) are also reviewed. Most patients had received a combination of topoisomerase II inhibitors (anthracyclines, mitoxantrone, or the epipodophillotoxin derivatives VP 16 or VM 26) and cyclophosphamide, which have also been implicated in the pathogenesis of secondary acute myeloid leukemia (AML) with 11 q23 rearrangements. These observations give further support to the existence of a subgroup of secondary acute leukemias with cytogenetic findings specific for de novo ALL and AML, especially those with translocations involving the 11 q23 region.     

Co-expression of two FAB-specific chromosome changes,t(15; 17) and t(8; 21), in a case of acute promyelocytic leukemia

 We describe a case of acute promyelocytic leukemia ANLL-M3 with association of t(15; 17) and t(8; 21) and various chromosomal aberrations. Clinically, immunologically, and morphologically, our patient fits the diagnosis of typical ANLL-M3. The co-existence of two specific FAB chromosomal translocations in a single leukemic clone is rare. The rarity of this association enhances the significance of this report. Received: 27 September 1995 / Accepted 13 March 1996     

Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk Acute Myeloid Leukemia (AML)

 Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy. Median age was 58 years (range: 18–76 years). Forty-nine patients (45%) achieved a complete remission (CR) after two induction cycles with idarubicin, ara-C, and etoposide, 52% of them aged ≤60 years and 35% aged >60 years (p=0.06). After two consolidation courses, patients were randomized to four cycles of either high- or low-dose IL-2. Patients aged up to 55 years with an HLA-identical sibling donor were eligible for allogeneic bone marrow transplantation. The median relapse-free survival was 12.5 months, with a probability of ongoing CR at 6.5 years of 19%. Overall survival of all patients was 8 months, and 21 months for the CR patients. Median survival was significantly longer among patients aged ≤60 years than among the older patients (16 vs 6 months, p<0.001). Median duration of survival and relapse-free survival were not statistically different in the two IL-2 treatment arms. Received: March 23, 1999 / Accepted: June 23, 1999     

Acute myocardial infarction in a patient with chronic myelogenous leukemia

 A case of acute myocardial infarction in association with chronic myelogenous leukemia is presented. The clinical management and possible reasons for the presentation are discussed. Received: 7 November 1995 / Accepted: 30 January 1996     

Paraneoplastic hypokalemia in acute myeloid leukemia: a case of renin activity in AML blast cells

 Hypokalemia due to renal potassium loss has frequently been observed in patients with acute myeloid leukemia (AML). The pathogenic mechanism for this hyperkaluresis is unclear. In this report we describe a patient with AML FAB M4, in whom the clinical course, the electrolyte disturbances, the serum aldosterone levels, and the diffuse hyperplasia of the adrenal cortex documented a typical case of marked secondary hyperaldosteronism. On analysis of the leukemic cells of this patient compared with normal bone marrow cells, a significant increase of renin-like activity in the cytosol of the blast cells was noted. Activation of the renin-angiotensin-aldosterone system by paraneoplastic production of renin-like activity in AML blast cells might contribute to the hypokalemia often observed in patients with acute myeloid leukemia. Received: 19 March 1996 / Accepted: 30 April 1996     

Plasmacytosis in acute myeloid leukemia: two cases of plasmacytosis and increased IL-6 production in the AML blast cells

 An increased plasma cell count in the bone marrow occurs in a subgroup of patients with acute myeloid leukemia (AML). The pathogenic mechanism for this plasmacytosis is unclear. In this report we describe two patients with AML and plasmacytosis who shared some features of their diseases. The morphological subtypes were AML M4 and M4eo; the leukemias were secondary to cytotoxic pretreatment, and complex cytogenetic changes were found in the leukemic cells of both patients. There was a marked increase in the number of bone marrow plasma cells in both cases and no monoclonal immunoglobulin was detectable. The IgH-CDR3 gene scan depicted a monoclonal IgH rearrangement in the bone marrow cells of one patient. Analysis of the cytokine production of the leukemic cells showed a high production of IL-6 of the leukemic blast cells in the in vitro cell culture and a high cytoplasmic IL-6 in the leukemic cells as revealed by immunocytology. We describe the clinical picture of a type of secondary AML with FAB M4 morphology associated with bone marrow plasmacytosis. We suggest that paracrine growth stimulation of plasma cells by paraneoplastic IL-6 production of the leukemic blast cells contributes to the plasmacytosis observed in patients with AML. Received: December 1, 1997 / Accepted: March 13, 1998     

Successful treatment with arsenic trioxide of a patient with ATRA-resistant relapse of acute promyelocytic leukemia

 Arsenic trioxide has recently been introduced as a promising new agent to treat refractory acute promyelocytic leukemia (APL). In the present study, arsenic trioxide was given intravenously for 42 days to a 56-year-old female patient suffering from chemotherapy/ATRA-resistant APL, with 43% APL blasts in the bone marrow and elevated D-dimers. During the first days of arsenic trioxide treatment a rapid decrease in the D-dimers was seen (normal values reached until day 7), together with a slight decrease in peripheral blood leukocytes. This initial coagulation response was followed by a second phase of hematological response (starting on days 15–20) characterized by leukocytosis, occurrence of myeloid progenitor cells in the peripheral blood, and a decrease in bone marrow blasts (<1% on days 28 and 36). Finally, the patient entered complete hematological and cytogenetic remission, although the PML-RARα fusion product was still detectable by PCR. These data confirm the therapeutic value of arsenic trioxide in relapsed/resistant APL. Received: February 10, 1999 / Accepted: March 29, 1999     

Alloantibody from a patient with severe von Willebrand disease inhibits von Willebrand factor-FVIII interaction

 Older patients with RAEB-T or AML are extremely difficult to treat. They are at high risk of infection and/or bleeding complications and have a low probability of cure and short overall survival with conventional treatments. We treated 12 patients with an outpatient low-dose chemotherapy regimen consisting of Ara-C 100 mg subcutaneously on day 1, and 6-thioguanine 80 mg orally on days 2–5, repeated every week. Nine patients had MDS, six RAEB-T, and three RAEB (median age 57 years) and three had de novo AML (median age 73 years). All patients were transfusion dependent. The mean peripheral blast count at the beginning of treatment was 29% (4–51%). The median follow-up is 13 months (2–34 months) for all the patients and 14 months (2–34 months) for those with RAEB-T. Nine of the 12 patients are alive, including seven RAEB-T patients with a median of 18 months (range 6–34+ months). During treatment, the peripheral blast count was markedly reduced to a mean of 5% (0–23%). The mean pre-therapy platelet count, with transfusion support, was 24.0×10⁹/l, while the mean post-therapy platelet count without transfusion support is 95.0×10⁹/l. All patients except two became transfusion independent at some time. Treatment for 6–10 weeks was required to show reduction of blast number and increase in hemoglobin, platelet, and WBC counts. Initial cytopenias were the only side effects of this regimen. One patient had granulocytopenic fever. In conclusion, this low-dose regimen is effective and well tolerated for outpatient palliation in high-risk or elderly patients with RAEB-T or AML. Received: 11 September 1996 / Accepted: 8 January 1997     

Chronic systemic aspergillosis in a patient with acute myeloid leukemia

 Systemic aspergillosis is a well-recognized complication of chemotherapy-induced neutropenia. In this report a patient with acute myeloid leukemia is described in whom a chronic aspergillosis with systemic involvement developed after recovery from neutropenia following intensive chemotherapy and allogeneic bone marrow transplantation. The clinical features of a chronic course of systemic aspergillosis suggest a distinct clinical entity comparable to chronic systemic candidiasis. Received: 13 November 1997 / Accepted: 11 February 1998     

Occurrence of T-cell lymphoma in a patient with acute myelogenous leukemia

 We describe a patient with AML with a monocytic component who developed a T-lymphoblastic lymphoma. Lymphoma was diagnosed 9 months following AML diagnosis. To our knowledge, this is the first report of phenotypically documented T-cell lymphoma following AML. The questions relating to the pathogenesis of the two malignancies are discussed. Received: 22 January 1996 / Accepted: 12 April 1996     

Pseudomonas aeruginosa blepharoconjunctivitis during cytoreductive chemotherapy in a woman with acute lymphocytic leukemia

 Patients undergoing chemotherapy regimens for hematologic malignancies are prone to develop unusual and potentially life-threatening infections during periods of leukopenia- induced immunosuppression. We report the case of a woman who received consolidation chemotherapy for acute lymphocytic leukemia and acquired necrotizing Pseudomonas aeruginosa blepharoconjunctivitis of the right eye during a period of mild leukopenia. The infection led to severe orbital and periorbital inflammation, spreading down to the neck. High-dose antibiotic treatment with ceftazidime and tobramycin combined with granulocyte cell-stimulating factor cleared the infection after several days, but plastic surgery was needed to restore normal eye closure. Received: 13 May 1997 / Accepted: 24 June 1997     

Acquisition of t(11;14) in a patient with chronic lymphocytic leukemia carrying both t(14;19)(q32;q13.1) and +12

A rare recurrent chromosomal translocation, t(14;19)(q32;q13), has been identified in a variety of B‐cell malignancies, including chronic lymphocytic leukemia (CLL). We report a unique case of CLL in a patient carrying both trisomy 12 and t(14;19) (q32;q13.1), in whom t(11;14)(q13;q32) developed at relapse. The patient was a 77‐yr‐old woman, and her lymphoma cells at presentation showed CD5⁺, CD10^?, CD19⁺, CD20⁺(dim), CD23⁺, CD38⁺, and CD11c⁺. At relapse, the patient's lymphoma cells showed positive staining for cyclin D1 in addition to CD5, CD20, and CD23. Lymphoma cells in specimens at both presentation and relapse were positive for lymphoid enhancer factor 1 (LEF1) and negative for sex‐determining region Y‐box 11 (SOX11). IGH‐BCL1 FISH became positive at relapse. Split FISH assay using BCL1, BCL3, IGH, and CCND1 probes on lymph node specimens obtained at presentation and at autopsy confirmed that the translocation of BCL3 was solely detected in the lymph node at presentation and detected BCL3 and CCND1 translocations in the specimen at autopsy. These observations indicated that IGH‐BCL3 and IGH‐CCND1 had occurred in the same clone after treatment of the disease. In line with immunohistochemical and cytogenetic studies, additional PCR analysis of the FR3‐JH region showed the same sequence derived from IGHV4‐34 in specimens obtained at disease onset and relapse.     

Palliative cytoreduction in refractory acute leukemia: a retrospective study of 57 adult patients

 The efficiency and toxicity of treatment regimens for nonintensive cytoreduction in 57 outpatients with refractory acute leukemia (mean age 56 years, 51 AML, six ALL/AUL) were retrospectively studied. Seventeen patients received one treatment regimen, 19 patients two treatment regimens, and 21 patients three or more treatment regimens. The treatment regimens analyzed were 6-thioguanine p.o. (daily) (T), 6-thioguanine p.o. (4–7 days/week) + cytarabine s.c./i.v. (once a week) (T+C), 6-mercaptopurine p.o. (daily) (MP), 6-mercaptopurine p.o. (daily) + methotrexate p.o./i.v. (once a week) (MP+MTX), etoposide p.o. (daily) (E), and mitoxantrone i.v. (M). The median leukocyte count was higher for M (73×10⁹/l) than for the other treatment regimens (T: 27×10⁹/l, T+C: 37×10⁹/l, MP: 24×10⁹/l, MP+MTX: 30×10⁹/l, E: 31×10⁹/l). A cytoreduction >50% in the peripheral blood was achieved by T in 11/19, by T+C in 7/11, by MP in 5/8, by MP+MTX in 3/6, by E in 3/4, and by M in 16/22 patients. The period of cytoreduction was regarded as the duration of response – T: median 53 days, range 5–98; T+C: median 61 days, range 14–226; MP: median 37 days, range 4–192; MP+MTX: median 58 days, range 36–59; E: median 121 days, range 26–159; M: median 39 days, range 8–78. T and T+C were well tolerated by all but three patients (stomatitis, diarrhea, WHO grade 2). MP was accompanied by a rise of transaminases (WHO 1–3) in 5/6 patients. E led to stomatitis (WHO 1,2) in 4/5 and M to nausea/vomiting (WHO 1,2) in 5/22 and to stomatitis (WHO 2) in 4/22 cases. The mean survival time after start of palliative cytoreduction was 16 weeks (2–65). In summary, 6-thioguanine ± cytarabine was best tolerated with effective but – in oral monotherapy – often protracted cytoreduction in 60% of patients. Mitoxantrone showed tolerable side effects and potent cytoreduction in 73% of patients even after ineffective palliative pretreatment. Palliative cytoreductive therapy does not reduce the quality of life and can prevent complications of significant leukocytosis in refractory acute leukemia. Received: April 8, 1999 / Accepted: August 9, 1999     

Involvement of the coronary artery in a patient with thromboangiitis obliterans. A case report

 We report a case of coronary artery bypass grafting (CABG) using the left internal mammary artery (LIMA) and a saphenous vein graft in a 36-year-old man with Buerger's disease. He was hospitalized in the coronary intensive care unit with a diagnosis of acute myocardial infarction. His coronary angiography showed total occlusion of the proximal segment of the left anterior descending artery (LAD) and right coronary artery. Left ventricular dysfunction was detected by ventriculography. The patient had undergone bilateral sympathectomy of the lumbar branches for distal arterial occlusions due to thromboangiitis obliterans 12 years previously. Under cardiopulmonary bypass and aortic cross-clamping, we performed endarterectomy and a complex bypass procedure to LAD. Aorta-right coronary artery bypass was also applied. A histopathological study of an endarterectomy specimen showed characteristic features of thromboangiitis obliterans. The postoperative course was uneventful and the patient was discharged on the ninth postoperative day. Received: November 19, 2001 / Accepted: February 16, 2002     

T-cell lineage acute lymphoblastic leukemia with chromosome 5 abnormality in a patient with Crohn's disease and lipoid nephrosis

 We describe a 17-year-old patient with a documented history of Crohn's disease (CD) and of minimal-change nephrotic syndrome (MCNS) in whom a diagnosis of T-cell acute lymphoblastic leukemia (ALL) was made. The diagnosis of ALL was established by morphological examination of bone-marrow aspirates and confirmed by means of immunophenotypic analysis showing the involvement of T-cell lineage leukemic cells. The lymphoid clone showed a karyotypic abnormality involving the long arm of chromosome 5 in a translocation (5;6). Few cases of CD complicated by ALL have been previously reported. The present one is the first case combining CD and ALL in a patient with a past history of MCNS. This raises the possibility of a relationship among those diseases. The possible mechanisms for such a relationship are discussed here. Received: June 25, 1999 / Accepted: September 9, 1999     

Splenic rupture in a patient with acute myeloid leukemia undergoing peripheral blood stem cell transplantation

 Splenic rupture is a rare but well-recognized complication of hematological malignancies. Here, we present the case of a 22-year-old woman with the diagnosis of acute myeloid leukemia who was undergoing peripheral blood stem cell transplantation. On day +10 she developed a hypovolemic shock due to rupture of her spleen and went to emergency laparotomy. This is the first report of splenic rupture during peripheral blood stem cell transplantation. Received: May 7, 1998 / Accepted: October 21, 1998     

急性髓系白血病患者原发性mdr1基因与CD34抗原表达及预后关系

应用RT－PCR技术对31例初诊急性髓细胞白血病（AML）患者mdr1基因进行检测、发现mdr1表达率为41．94％；AML亚型中以M5的mdr1表达率最高，M3最低；mdr1表达与临床患者耐药发生率显著相关。同时应用一级相关单抗，采用碱性磷酸酶抗碱性磷酸酶方法分析了患者细胞免疫标记与mdr1表达及预后的关系，结果显示，CD34与mdr1协同表达者耐药发生率更高。提示进行mdr1基因表达检测的同时，观察CD34表达情况，可能对预测化疗效果有意义。     

Rapid tumor lysis in a patient with B-cell chronic lymphocytic leukemia and lymphocytosis treated with an anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab)

Summary In this report we present a patient with B-cell chronic lymphocytic leukemia who developed an acute tumor lysis syndrome after administration of the human anti-CD20 antibody IDEC-C2B8 (RITUXIMAB) in standard dose of 375 mg/m². IDEC-C2B8 has been demonstrated to have only mild and tolerable side effects in patients with follicular lymphoma. In these trials patients with lymphocytosis >5000/μl were excluded. Physicians must be aware of this hitherto unreported phenomenon in patients with high CD20-positive blood counts. Received: July 9, 1998 / Accepted: July 20, 1998