1/92. Jumping translocations involving chromosome 1q in a patient with crohn disease and acute monocytic leukemia: a review of the literature on jumping translocations in hematological malignancies and crohn disease. A 36-year-old man with a 10-year history of crohn disease (CD) presented with gross hematuria and blasts in his peripheral blood. A chromosome analysis revealed one normal cell and 33 abnormal cells. The stem line was 47,XY, 8. The multiple side lines also had a jumping translocation between chromosome 1q31-32 and 4, 8, 10, 17, and 18 terminal regions. A cytogenetic, morphologic, and immunophenotypic analysis of a bone marrow aspirate and biopsy demonstrated acute myeloid leukemia of monocytic lineage, AML-M5b. In this paper are reviewed (a) the unusual and rare phenomenon of jumping translocations in hematological malignancies and (b) leukemia in CD. ( info) |
2/92. Secondary hemochromatosis as a long-term complication of the treatment of hematologic malignancies. The increased cure rate of hematologic malignancies including the use of bone marrow transplantation has focused attention on the chronic toxicity and quality of life of the survivors. We have observed five patients who have been diagnosed with clinically significant iron overload, presumably due to packed red blood cell transfusions, >/=12 months after transplant for a hematologic malignancy. In these patients, there is no history of veno-occlusive disease or family history of hemochromatosis. The allotransplant patient has been free of chronic graft versus host disease. family screening has been negative. No patient developed clinically significant endocrinopathy, arthropathy, or cardiac disease. The patients have been treated with phlebotomy to bring the transferrin saturation and ferritin levels to normal. The long-term follow-up of patients treated for a hematologic malignancy should include analysis of hepatitis c virus and iron status. This may prevent the development of clinically significant chronic liver disease and possibly malignancy. ( info) |
3/92. High-dose corticosteroid therapy for diffuse alveolar hemorrhage in allogeneic bone marrow stem cell transplant recipients. In a series of 74 patients with hematological malignancies undergoing allogeneic bone marrow or peri- pheral blood stem cell transplants from an HLA-identical sibling donor, four developed diffuse alveolar hemorrhage (DAH) between days 0 and 23 post transplant. diagnosis was made by the radiographic finding of diffuse bilateral lung opacities, and bloody lavage fluid on bronchoscopy. Two patients required mechanical ventilatory support. They were treated with methylprednisolone 0.25-1.5 g/day for at least 4 days with slow tapering thereafter. All patients showed an immediate response and two became long-term survivors with normal respiratory function. Two had a relapse of DAH, developed acute respiratory distress syndrome (ARDS) and died with multi-organ failure. risk factors for DAH were one or more courses of intensive chemotherapy pretransplant vs no treatment or low-dose chemotherapy (4/4 DAH vs 23/70 no DAH; P = 0.015), and second transplants (2/2 DAH vs 1/70 with no DAH; P = 0.006). These results indicate that DAH is life-threatening but is potentially reversible by prompt treatment with high doses of steroids. ( info) |
4/92. Late onset veno-occlusive disease following high-dose chemotherapy and stem cell transplantation. The original definition of hepatic veno-occlusive disease (VOD), which is still widely accepted, includes onset of the clinical syndrome before day 20 following high-dose chemotherapy (HDC) and stem cell transplantation (SCT). We retrospectively identified four patients following HDC and SCT presenting with late onset VOD occurring at day 24, day 27, day 34 and day 42 post SCT. All patients had moderate VOD, with successful resolution of the VOD before day 100 with optimal supportive therapy. Common risk factors for VOD shared by all four patients included an older age (median age: 60 years), and use of a busulphan-containing regimen. Mean and maximum bilirubin levels for all patients during the VOD syndrome were 2.02, 1.76, 5.09, 2.87 mg/dl and 2.5, 2.2, 8.9 and 4.1 mg/dl, respectively, which correlated well with duration of VOD. All patients encountered platelet transfusion-dependent thrombocytopenia during VOD. ursodeoxycholic acid was used as VOD prophylaxis beginning at a mean of 33 days prior to onset of VOD. As the cellular target of hepatic VOD is as yet unidentified, it is uncertain whether ursodiol or other common characteristics of patients with late onset VOD influence the pathogenesis and natural history of this disease. We believe that the uncommon clinical entity of late onset VOD, a potentially fatal regimen-related toxicity, should not be ignored as a diagnosis of liver disease after 3 or more weeks following HDC and SCT. ( info) |
5/92. Biphenotypic hematological malignancy with T-lymphoid and myeloid differentiation: association with t(3;12)(p25;q24.3). Case report and review of the literature. Biphenotypic hematological malignancies of T-lymphoid and myeloid differentiation are relatively rare and have most commonly been associated with t(8;13). However, this entity is invariably associated with eosinophilia and generally progresses to acute leukemia within a year of diagnosis. We describe a case of a biphenotypic hematological malignancy with T-lymphoid and myeloid differentiation without associated eosinophilia; however, there was an association with t(3;12)(p25;q24.3) as a sole abnormality and progression to acute leukemia within 10 months of presentation. This association with such a malignancy has not previously been described. Additional cases need to be accrued to determine the prognostic significance and clinical implications of such an association. ( info) |
6/92. Use of rituximab and irradiated donor-derived lymphocytes to control Epstein-Barr virus-associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation. Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is an uncommon but potentially fatal complication of allogeneic stem cell transplantation. We report here two patients who underwent T cell-depleted mismatched-related stem cell transplantation for hematologic malignancies and required aggressive post-transplant immunosuppression for graft-versus host disease (GVHD). Both patients subsequently developed markedly elevated EBV-dna titers in association with monoclonal, light chain-restricted B cell populations in the blood. Although immunosuppressive medications were rapidly tapered, neither patient could receive potentially curative therapy with unmanipulated donor-derived lymphocyte infusions (DLI) because of the substantial risk of severe GVHD. Therefore, both patients received repeated courses of rituximab, an anti-CD20 monoclonal antibody, in combination with irradiated DLI. This therapeutic strategy resulted in normalization of the elevated EBV-dna titers and disappearance of the monoclonal B cell populations. Our results suggest that rituximab and possibly irradiated DLI played an important role in controlling early EBV-LPD in these two patients and may be an effective alternative therapeutic strategy for patients who develop EBV-LPD post transplant and are unable to receive unmanipulated DLI. ( info) |
7/92. Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21). The reciprocal translocation t(1;3)(p36;q21) is associated with myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and a poor prognosis. As yet no molecular genetic analyses of the t(1;3) have been reported. In four patients with t(1;3), all of whom had AML-M4, which evolved from MDS, the breakpoints at 3q21 clustered within a 60-kb region centromeric to the breakpoint of the inv(3)(q21q26), whereas the breakpoints at 1p36 clustered within a 90-kb region at 1p36.3. The presence of novel clusters in both the 3q21 and 1p36 breakpoints (BCRs) suggests a common, underlying molecular mechanism for the development of t(1;3)-positive MDS/AML. The Ribophorin I (RPN1) gene close to the BCR at 3q21 was highly expressed without gross structural changes, whereas the GR6 gene located within the BCR at 3q21 was not expressed. No other highly expressed genes were isolated in a 150-kb region at 3q21. Thus, it is likely that a gene at 1p36.3 is activated by the translocation of the 3q21 region or a gene important for transformation lies on 3q21, outside the 150-kb region. Further characterization of the BCRs at 1p36.3 and 3q21 should provide important insights into the molecular genetic mechanisms involved in the genesis of t(1;3)-positive MDS/AML. genes chromosomes Cancer 27:229-238, 2000. ( info) |
8/92. trisomy 15, sex chromosome loss, and hematological malignancy. We report 6 patients with myelodysplasia who, on routine cytogenetic studies, demonstrated trisomy 15. Four of these also had sex chromosome loss. A review of the literature revealed 6 other cases of trisomy 15 with sex chromosome loss and 22 cases of trisomy 15 as the sole chromosomal abnormality. All cases had hematologic malignancy or myelodysplasia. trisomy 15 is uncommon but tends to be associated with myelodysplasia in older subjects, and with sex chromosome loss in about one third of cases. ( info) |
9/92. Autoimmune liver disease in patients with neoplastic diseases. BACKGROUND: Development of de novo autoimmune liver disease has not been well documented in patients with malignant diseases. methods/RESULTS: In this paper we report on a series of six patients with neoplastic disorders who acquired liver disease with autoimmune features. Five patients had suffered from haematological neoplasms and one from colonic cancer. In two patients, liver disease was detected at the time of presentation with malignancy. In the remaining four, all of whom were successfully treated for malignancies, features of liver disease presented at intervals 24-72 months after the cancer diagnosis. Twelve liver specimens (11 biopsies and one hepatectomy specimen) were obtained at time intervals of 1-76 months after initial presentation of neoplastic disease. Biopsies from three patients showed features of hepatitis (one acute, one sub-acute, one chronic). Two patients had histological features suggestive of an overlap syndrome (one autoimmune hepatitis/primary biliary cirrhosis, one autoimmune hepatitis/primary sclerosing cholangitis). The sixth patient had features of autoimmune cholangiopathy. All but one responded well to steroid therapy with complete clinical and biochemical remission obtained 4 weeks to 8 months after steroid introduction. We discuss briefly possible aetiologies of autoimmune liver disease in these patients. CONCLUSIONS: Autoimmune liver disease may be precipitated by therapy for neoplastic disease or malignant disease itself. The unusually heterogeneous clinicopathological findings in this group as well as the response to treatment support the concept of a wide spectrum of manifestations of autoimmune liver disease. The results may also suggest that autoimmune liver disease may be possibly added to the list of paraneoplastic syndromes. Further prospective studies are required to confirm a causal association and to determine whether the mechanisms involved are disease- or treatment-related. ( info) |
| We present the case of a patient with acute myeloid leukemia and secondary pulmonary alveolar proteinosis (PAP), which is an underestimated cause of a persistent pulmonary infiltrate in patients with hematologic malignancies often accompanied by neutropenia due to therapy. diagnosis is established by performing periodic acid-schiff reaction (PAS) stains and transmission electron microscopy (EM) on bronchoalveolar lavage (BAL) fluid. We wish to stress the importance of the early recognition of PAP, which is potentially reversible, and routinely performing PAS staining on BAL fluid in patients with a hematologic disease especially myeloid disorders and a persistent lung infiltrate. ( info) |