Haruo Niikura

Transition of Polycythemia Vera to Chronic Neutrophilic Leukemia

Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl rearrangement. Busulfan was temporally effective in controlling the neutrophil count. However, one patient progressed to the so-called spent phase and the other subsequently had multiple transitions between PV and CNL. These cases may represent a form of uncommon evolution of PV and support the contention that CNL is a type of myeloproliferative disorder and that at least some CNL cases have derangement at the hematopoietic stem cell level.

Hypocomplementemia and Hematological Abnormalities in Immunoblastic Lymphadenopathy and Immunoblastic Lymphadenopathy-Like T Cell Lymphoma

Serum complement levels and hematological data were evaluated in five patients with immunoblastic lymphadenopathy (IBL) and four with IBL-like T cell lymphoma (IBL-T). Anemia with Hb values below 10.0 g/dl was seen in four patients. A direct Coombs test was positive in five patients and the bone marrow of two of these showed features of pure red cell aplasia. Seven patients were thrombocytopenic with platelet counts below 100 x 10(9)/l. Six of the seven patients had splenomegaly. Platelet-associated IgG was elevated in all three thrombocytopenic patients examined. Whole complement activity (CH50) was reduced in eight patients (89%) at presentation and subsequently normalized in five who were treated either with prednisolone (two patients with IBL) or with multidrug combination chemotherapy (three with IBL-T). One patient achieved complete remission and four partial remission. Remission was accompanied by normalization of hematological abnormalities and elevation of complement activity to the normal range in all cases. These results suggested that complement-mediated mechanisms are responsible, at least in part, for some of the hematological abnormalities observed in IBL and IBL-T and that hypocomplementemia is a common abnormality with significance as a laboratory marker for the disease activity.

CASE REPORT: Primary hepatic lymphoma associated with chronic liver disease

We report on a case of primary hepatic lymphoma that developed in a patient with chronic hepatitis C. Given that Japan is an area endemic for both hepatitis B and C viruses, we reviewed 51 Japanese cases of primary hepatic lymphoma, addressing the question as to whether the Japanese cases have unique characteristics and whether there is a causal relationship to the presence of chronic liver disease. Primary hepatic lymphoma most commonly affected middle‐aged males. Presenting symptoms and physical findings were non‐specific. Aminotransferases tended to stay in the low range compared with marked increases in lactate dehydrogenase. Sixteen patients (31%) had chronic liver disease, eight had liver cirrhosis and eight had chronic hepatitis, suggesting that there is a possible aetiological link between chronic liver disease and primary hepatic lymphoma.

Disseminated intravascular coagulation complicating acute lymphoblastic leukemia: A study of childhood and adult cases

A high incidence of disseminated intravascular coagulation (DIC) in adult patients with acute lymphoblastic leukemia (ALL) is reported. However, studies comprising both childhood and adult patients are sparse and the clinical relevance of DIC in ALL patients has been a conflicting issue. Coagulation profiles at presentation and within seven days after starting remission-induction therapy of 44 childhood and 51 adult ALL patients were studied. At presentation, two childhood (5%) and 11 adult (22%) patients had DIC (p<0.05). After starting therapy, four of 27 childhood (15%) and 14 of 33 adult (42%) patients screened for coagulopathy developed DIC (p<0.05). Overall, six of the 44 children (14%) and 25 of the 51 adults (49%) were complicated with DIC (p<0.001). In the adult cases, DIC was more frequently complicated with FAB subtype L2 than L1 (p<0.05). All hemorrhages seen in the childhood cases were minor hemorrhages. In the adult patients, two patients with DIC had WHO grade 3 hemorrhage and the other hemorrhagic complications were minor hemorrhages. While milder induction therapies starting with corticosteroid given for childhood cases should be taken into consideration when comparing the incidences of DIC after therapy, the findings indicated that childhood and adult ALL may differ in the procoagulant characteristics. Morphological distinction between L1 and L2 appears to have relevance in the procoagulant activity in adult ALL. DIC complicating ALL is generally mild, however, sometimes causes severe hemorrhages in adults.

Disseminated intravascular coagulation in acute lymphoblastic leukemia at presentation and in early phase of remission induction therapy

Abstract A high frequency of disseminated intravascular coagulation (DIC) in adult acute lymphoblastic leukemia (ALL) has been reported; however, its clinical relevance and characteristics have not been fully determined. We studied 67 adults with newly diagnosed ALL between 1982 and 1996 to clarify these questions. DIC was diagnosed in ten of 64 patients (16%) who underwent coagulation study at presentation and in 14 of 40 patients (35%) screened for DIC within 7 days after starting remission induction therapy. Overall, 24 of 67 patients (36%) had DIC during this period. Hemorrhagic symptoms were generally mild, while two patients required red blood cell transfusions. Patients who developed DIC had higher white blood cell counts and more frequently a palpable spleen than those who did not. There was no difference in age, French-American-British subtype, karyotype, immunophenotype, lactate dehydrogenase level, percentage of blasts in bone marrow, or frequency of lymphadenopathy or hepatomegaly between patients who had DIC and those who did not. Fibrinolysis tended to be milder in DIC complicating ALL than in that complicating acute promyelocytic leukemia; however, there was no difference in other coagulation parameters between these two subtypes. An etiological link between CD34 expression in common ALL patients and DIC was suggested.

Cytogenetics, FISH and RT-PCR Analysis of Acute Promyelocytic Leukemia: Structure of the Fusion Point in a Case Lacking Classic t(15;17) Translocation

The chimeric gene product PML-RAR α, the result of a reciprocal t(15;17) translocation, plays an important role in the pathogenesis of acute promyelocytic leukemia (APL). In the present study on clinical effects of cytogenetics and molecular events in APL, we performed chromosome analysis, fluorescence in situ hybridization (FISH) using gene-specific probe, and reverse transcription-polymerase chain reaction (RT-PCR) analysis in 10 patients with APL. Patients were treated with all- trans retinoic acid (ATRA) and/or chemotherapy, and all achieved complete remission. Cytogenetic analysis revealed the classic translocation t(15;17) in nine of 10 patients, and a remaining patient had an apparently normal karyotype. Interphase FISH was performed in nine patients, and revealed the presence of PML-RAR α fusion gene in all patients. RT-PCR analysis in 10 patients showed that eight expressed long (L)-form type, one expressed a short (S)-form type, and the other expressed a variable (V)-form type. Metaphase FISH of the patient with normal karyotype revealed a juxtaposed PML-RAR α fusion signal on one chromosome 17 homologue, an RAR α signal on the other chromosome 17 homologue, and one PML signal on each chromosome 15 homologue. Moreover, V-form of the PML-RAR α transcript was detected, and a portion of RAR α intron 2 was found inserted in the breakpoint region. ATRA differentiation induction therapy was effective in treating this patient, a result infrequently reported in cytogenetic and molecular investigations of APL.

Coagulation patterns of disseminated intravascular coagulation in acute promyelocytic leukemia.

Coagulation patterns of 19 newly‐diagnosed acute promyelocytic leukemia (APL) patients with disseminated intravascular coagulation (DIC) at presentation were studied. Seventeen patients had hemorrhagic complications, of which four were fatal. Fatal hemorrhages were related with lower fibrinogen level and lower platelet count. DIC of the APL patients without infection was characterized by low fibrinogen and normal antithrombin III (ATIII) level. Thrombin–ATIII complex level was elevated in all patients examined. Patients with infection had higher fibrinogen levels than those without infection and some patients had reduced ATIII level. Ten remission inductions were tried with multidrug chemotherapy and seven with all‐trans retinoic acid (ATRA). Complete remission was achieved in seven of ten inductions with chemotherapy and in all seven inductions with ATRA. Two patients treated with chemotherapy had fatal hemorrhage after starting therapy but none treated with ATRA.

Molecular cloning of t(2;7)(p24.3;p14.2), a novel chromosomal translocation in myelodysplastic syndrome-derived acute myeloid leukemia

In this study, we report the molecular structure of the breakpoint region in a new chromosomal translocation, t(2;7)(p24.3;p14.2), in a case of acute myeloid leukemia transformed from myelodysplastic syndrome (MDS). An extensive fluorescence in situ hybridization (FISH) analysis showed that NAG (2p24.3) and ELMO1 (7p14.2) were involved at the breakpoints of t(2;7)(p24.3;p14.2). Furthermore, we detected a novel chimeric transcript consisting of NAG and ELMO1. Interestingly, this transcript encoded a truncated molecular form of 3′ELMO1 as the result of a frameshift caused by the chromosomal translocation. Although this study does not provide direct evidence that a defect in NAG-ELMO1 plays a role in the pathogenesis or the leukemic change in MDS, it does suggest that defects in NAG-ELMO1 potentially contributed to the leukemic progression in this case.

Immunoblastic Lymphadenopathy-Like T Cell Lymphoma Evolving into a Massive Plasma Cell Proliferation with Biclonal Paraproteinemia

We present a case of immunoblastic lymphadenopathy-like T cell lymphoma (IBL-T) who subsequently developed a massive proliferation of plasma cells. At diagnosis of IBL-T, the patient had polyclonal hypergammaglobulinemia and subsequently, while on chemotherapy, developed paraproteinemia with biclonal peaks and the IBL-T lesion was replaced with a massive proliferation of CD38-positive plasma cells. The evolution was not likely to be attributed to a new neoplastic proliferation of B cells. It appeared that two B cell clones possibly had a growth advantage among the polyclonal B cells due to a depletion of suppressor T cells or to a disturbance in the immune system.

Paroxysmal Nocturnal Hemoglobinuria in Association with Chronic Myelofibrosis

Two cases of chronic idiopathic myelofibrosis (CIMF) associated with paroxixmal nocturnal hemoglobinuria (PNH) are descrived. Case 1 was 60 yrs old male. He was diagnosed CIMF in 1990. Association of PNH was diagnosed in 1995. PNH clone expand gradually, frequent hemolytic episodes were observed. He died by liver failure in 1999. Case 2 was 51 yrs old male. He was daiagnosed as CIMF in 1993 and association of PNH was diagnosed in 2000. Case 2 has no typical hemolytic episode so far. Since both diseases belong to clonal diorder, it is suggested clonal evolution was occurred in CIMF and developed PNH.