Successful treatment of post-MRSA infection glomerulonephritis with steroid therapy.

A 48-year-old man without underlying disease developed mediastinitis and was treated by mediastinal drainage. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in a culture of the abscess material. He was treated with anti-MRSA antibiotics and the MRSA infection improved. Four weeks after the onset of MRSA infection, he developed rapidly progressive glomerulonephritis (RPGN) with nephrotic syndrome (NS). A renal biopsy showed endocapillary proliferative glomerulonephritis with IgA-predominant glomerular deposition. These clinicopathological findings were consistent with those in glomerulonephritis following MRSA infection (post-MRSA infection glomerulonephritis). The level of serum creatinine increased to 6.3 mg/dl, 7 weeks after the onset of RPGN. At that time, the eradication of MRSA infection was considered. He was given middle-dose steroid therapy. Thereafter, his RPGN with NS improved. MRSA infection did not recur. If the disease activity of post-MRSA infection glomerulonephritis persists after the disappearance of MRSA infection, the application of immunosuppressive therapy with steroids may be useful.

A PML/RARA chimeric gene on chromosome 2 in a patient with acute promyelocytic leukemia (M3) associated with a new variant translocation: t(2;15;17)(q21;q22;q21).

We describe a patient with acute promyelocytic leukemia (APL) carrying a new complex variant translocation of t(2;15;17)(q21;q22;q21). The karyotypic interpretation was confirmed by fluorescence in situ hybridization (FISH) with the use of painting probes of chromosomes 2, 15, and 17 and a PML/RARA dual color DNA probe. FISH showed a PML/RARA fusion gene on the der(2) instead of the der(15). These results suggest that the critical event in the development of APL is the formation of a PML/RARA chimeric gene, regardless of its locus in the genome.

[Autologous peripheral blood stem cell transplantation for CHOP-resistant mediastinal diffuse large B-cell lymphoma].

We report two cases of CHOP-resistant mediastinal diffuse large B-cell lymphoma (MDLCL) treated by autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were 17 and 28 year old female, and they had anterior mediastinal bulky masses at presentation. The clinical stage was IV in both patients. They were initially treated with 6 courses of bi-weekly CHOP therapy following by irradiation of the mediastinal tumors. During the last few cycles of CHOP therapy, their disease had become progressive. They underwent auto-PBSCT after high-dose chemotherapy consisting of busulfan, cyclophosphamide and etoposide, but failed to achieve remission. They died within one year after the auto-PBSCT because of the disease progression. Our experience suggests that this conditioning regimen is not effective for CHOP-resistant MDLCL, and it is necessary to develop new conditioning regimens.

Autoantibodies against 70-kDa heat shock proteins (HSP70) in allogeneic bone marrow transplant recipients.

We report that autoantibodies against the 70-kDa heat shock protein family (HSP70) were detected in allogeneic bone marrow transplant recipients. Antibodies to HSP70 family proteins were detected in three out of 14 recipients of an allogeneic marrow graft but in none of the seven patients receiving autologous peripheral blood stem cell transplant (PBSCT). Immunoblotting analysis combined with two-dimensional SDS-PAGE revealed that these patients had antibodies to a constitutive 73-kDa/pI 5.5 heat shock protein (HSP73) and to a stress-inducible 72-kDa/pI 5.6 protein (HSP72). This is the first report, to our knowledge, describing the presence of autoantibody against HSP73 in allogeneic marrow transplant recipients. Our results may provide additional insight into the etiology and the pathophysiology of allogeneic transplant-related disorders.

Extramedullary megakaryoblastic tumors following an indolent phase of myelofibrosis.

A 59-year-old man developed multiple subcutaneous and bone tumors after 2 years' duration of indolent myelofibrosis. These tumors exhibited a diffuse proliferation of pleomorphic blast cells. The skeletal x-rays showed disseminated osteolysis and osteosclerosis. Blast cells obtained from the pleural effusion did not react with myeloperoxidase, sudan black B or non-specific esterase. Genotypic analysis of DNA samples at autopsy did not demonstrate rearrangements of T-cell receptor beta-chain or immunoglobulin heavy-chain genes. Frozen-section immunohistochemical studies revealed that the neoplastic cells were derived from megakaryocytic lineage. The present case represents a novel and unusual subtype of megakaryocytic neoplasm.

Syndrome of inappropriate secretion of antidiuretic hormone in patients with lymphoma-associated hemophagocytic syndrome.

We report three lymphoma patients in whom the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was observed during the course of lymphoma-associated hemophagocytic syndrome (LAHS). The clinical course was devoid of any known mechanism for SIADH which could be attributable to lymphoma or antineoplastic treatment. Alternatively, high serum levels of interleukin-1 beta and tumor necrosis factor-alpha, which stimulate the secretion of antidiuretic hormone, may have contributed to the development of SIADH in our patients, who were receiving glucocorticoids. In conclusion, LAHS patients should be considered to be at high risk for SIADH.

Risk factors for hepatosplenic abscesses in patients with acute leukemia receiving empiric azole treatment.

The authors retrospectively evaluated 63 febrile neutropenic episodes in 33 consecutive patients with leukemia who received empiric azole treatment for refractory or relapsing fever that occurred despite broad-spectrum antibiotics. In 8 patients (24%), hepatosplenic abscesses (HSA) developed. To identify the risk factors for the development of HSA, the authors compared various characteristics of febrile episodes in those with and without HSA. The risk factors included relapsed status of leukemia (P = 0.04) and Candida colonization of surveillance cultures from the throat (P = 0.03) and stool (P = 0.03). However, the duration of neutropenia, gastrointestinal symptoms, types of chemotherapy, and leukemia subtypes were not correlated with the development of HSA. Based on these results, the authors identified the high risk group for the development for HSA as patients with relapsed leukemia with fungal colonization of gastrointestinal tract during neutropenia despite empiric antifungal treatment with azoles.

Successful vidarabine therapy for adenovirus type 11-associated acute hemorrhagic cystitis after allogeneic bone marrow transplantation.

A 36-year-old man underwent an allogeneic BMT for acute lymphoblastic leukemia. Eighteen days later the patient developed sudden onset of painful, gross hematuria due to adenovirus type 11 infection that did not respond to conservative therapy. There was an increase in serum creatinine levels and delayed recovery of the platelet count, associated with hemophagocytosis. After obtaining informed consent, vidarabine, which has been shown to be active against adenovirus in vitro, was started. The patient's symptoms improved within a few days of vidarabine therapy and urine cultures for adenovirus became negative. No serious adverse effects were observed. Vidarabine may be one therapeutic option in life-threatening adenovirus infection.

Translocation (8;17)(p21;q21), a possible variant of t(15;17), in acute promyelocytic leukemia.

We report a 64-year old man with typical features of acute promyelocytic leukemia (APL) [M3, French-American-British (FAB) classification] in whom a variant, t(8;17)(p21;q21), was detected. This is the second case of the same variant translocation to be reported. The breakpoint on 17q was similar to those described in cases with a standard translocation 15;17. Consequently, this chromosome break or rearrangement at band 17q21, rather than the recipient site of translocation of the deleted material, appears to be of crucial importance in the genesis of APL.

[Long term follow-up of three cases of acute myeloid leukemia associated with inv(16)(p13q22)].

Three cases of acute myeloid leukemia associated with inv(16(p13q22) were followed up for over 5 years. This chromosome aberration is generally thought to be a good prognostic factor. However, it is also reported that these patients are apt to relapse and have relatively high frequency of central nervous system (CNS) involvement. The first patient (M4Eo), who died of gastric cancer about 5 years after the initial treatment without frank relapse, did not have prophylactic therapy for CNS involvement. The second patient (M5b) developed meningeal leukemia and myeloblastoma of the brain, showing similar findings on CT scan to cases reported by Holms et al. He was treated successfully with whole brain irradiation and intrathecal injection of ara-C and MTX, and intracranial tumor disappeared on CT and MR imaging. He has been enjoying a good quality of life without any complication for over ten years after the initial diagnosis. The third patient (M4Eo) relapsed once but reentered complete remission with relative ease and we used an intrathecal injection prophylactically. This case has been followed up as an outpatient for more than 5 years since onset. On the basis of these findings, it may be concluded that these leukemia patients with inv(16)(p13q22) have good prognosis and can be cured with chemotherapy.

[Proliferation of micromegakaryocytes in acute myelocytic leukemia associated with 5 q- as the sole karyotypic abnormality].

The authors report a de novo AML (M2) patient associated with 5q- as the sole karyotypic abnormality. A 76-year-old woman was referred to our hospital because of anemia and leukocytosis. On examination a neck lymph node was enlarged, but neither the liver nor the spleen could be palpated. The hemoglobin level was 7.1g/dl, the mean corpuscular volume 102fl and the white-cell count was 256.1 x 10(3)/microliters with 87% blast cells. The platelet count was 10.9 x 10(4)/microliters. The bone marrow was hypercellular with 79.8% blast cells and showed dysmegakaryocytopoietic features (hypolobulation, multiple separated nuclei and micromegakaryocytes). Blast cells gave a positive reaction for peroxidase and alpha NB esterase which was not blocked by NaF. The diagnosis of AML (M2) was made but she died before chemotherapy. Autopsy revealed general hemorrhagic tendency and leukemic cell infiltration. Chromosome analysis of the bone marrow showed 46,XX,del(5) (q13q31). Electron micrographs revealed increase of micromegakaryocytes as small as myelocytes and aggregation of demarcation membranes in some megakaryocytes. This may suggest that some molecular changes, instead of karyotypic evolution, contributed to a leukemic transition from the 5q- syndrome to AML with 5q- as the sole abnormality.

Ph+ acute myelogenous leukemia with t(7;11)(p15;p15) and clonal evolution in relapse after bone marrow transplantation.

A 20-year-old female with Ph+ acute myelogenous leukemia (M2) associated with t(7;11)(p15;p15) is reported. Bone marrow aspirates were hypercellular with leukemic cells including Auer rods. Chromosome analysis showed t(7;11) and the Ph chromosome. After complete remission, normal karyotype was restored. Normal male karyotypic cells replaced the bone marrow following allogeneic bone marrow transplantation from her brother. On day 358, cytogenetic study at relapse revealed 14q+ as an additional change and clearly showed that the abnormal clone was derived from the patient, because metaphases with XX were all of abnormal karyotype and those with XY were normal.

[Isolated cerebellar tumor formation in a patient with blastic crisis of chronic myelogenous leukemia].

A 42-year-old male was diagnosed as having Ph-positive chronic myelogenous leukemia (CML) in 1988. He had been treated with ranimustine and interferon alpha. In April 1990, he was admitted to our hospital because of hemorrhagic diathesis. Blood counts revealed a white blood cell count of 319,200/microliters with 12 per cent blasts, a hemoglobin level of 9.2 g/dl, and a platelet count of 48,000/microliters. The bone marrow aspiration revealed hypercellularity with 68.2 per cent blasts, and chromosomal analysis showed 48, XY, +8, double Ph. A combination chemotherapy containing vindesine, cytarabine and prednisolone was administered. Four days later, he suddenly complained of headache and vertigo. CT scan of the brain showed a high density area at the cerebellar vermis. He was then treated with intensive combination chemotherapy including enocitabine, daunomycin, 6-mercaptopurine and prednisolone. He attained a hematological response and clinical improvement temporarily, as the cerebellar tumor regressed. In September he had headache and vertigo again, and CT scan revealed a rapid increase in size of the cerebellar tumor. Local irradiation with total doses of 19 Gy brought about a partial resolution of the lesion, and relief from the symptoms. In November, his hematological conditions deteriorated gradually and he died of brain hemorrhage on November 22, 1990. Post-mortem examination disclosed a 1 x 1 cm sized mass in the cerebellar vermis which showed a fibrous change surrounded with hemosiderin-laden macrophages microscopically. We reviewed the eight reported cases of CML with intracranial tumors, and discussed the factors which had contributed to the prolongation of survival in our patient.

[B-cell chronic lymphocytic leukemia complicated by autoimmune thrombocytopenic purpura].

A 74-year-old Japanese male was admitted because of anemia. Hepatosplenomegaly, lymphoadenopathy, and purpura were not found. The laboratory data on admission revealed that the white-cell count was 9,400/microliters, the hemoglobin 11.1 g/dl, and the platelet count 17,000/microliters. Platelet-associated IgG was 794.2 ng/10(7) cells. The patient was diagnosed as having autoimmune thrombocytopenic purpura (ATP) at this time. He was treated with prednisolone, but his thrombocytopenia not improve. In addition to prednisolone, azathioprine was given to him. During the course of treatment, leukocytosis gradually appeared and the white-cell count reached more than 30,000/microliters with over 70% lymphocytes. A bone marrow aspiration revealed 70% of small lymphocytes, and surface marker analysis showed that CD19 and HLA-DR were positive on these lymphocytes. Southern blotting analysis demonstrated rearrangements of JH and JK. He was finally diagnosed as B-CLL complicated by ATP. One month after the azathioprine administration, the platelet count increased more than 30,000/microliters and the white-cell count decreased less than 10,000/microliters. About 2% of patients with CLL are known to be complicated by ATP. To our knowledge, the present case is the first case of B-CLL complicated by ATP in Japan.

Inappropriate secretion of antidiuretic hormone in isolated adrenocorticotropin deficiency.

A 62-year-old man was admitted because of nausea and vomiting. Severe hyponatremia with renal sodium loss was found. Endocrinological studies revealed that the patient had isolated adrenocorticotropin (ACTH) deficiency and secondary adrenocortical insufficiency. Furthermore, an inappropriate secretion of antidiuretic hormone (ADH) in relation to the low plasma osmolality was observed at an early stage of hyponatremia. Hydrocortisone therapy effectively corrected his hyponatremia. Following the correction of hyponatremia, the value of free water clearance increased and the level of the plasma ADH decreased. Thus, the present case indicates that ACTH deficiency can cause the syndrome of inappropriate secretion of ADH.

Serum tumor necrosis factor-alpha levels in allogeneic bone marrow transplant recipients with acute leukemia.

We determined the serum levels of tumor necrosis factor-alpha (TNF) in allogeneic bone marrow transplant recipients in order to evaluate the relationship between TNF and graft-versus-host disease (GVHD). Eight patients with acute leukemia receiving an HLA-identical marrow graft were studied. Samples from healthy subjects and pretransplant recipients were all negative for TNF. Six of eight patients had detectable levels of TNF in serum after transplantation. All three patients with acute GVHD, and three of five patients without acute GVHD had elevated TNF levels in serum. Among the patients with increased TNF levels, documented infection was demonstrated in only one patient, with a clinical diagnosis of B19 parvovirus infection. Serum TNF levels were elevated when the WBC counts were more than 2,000/microliters. However, serum concentrations of TNF significantly correlated with body temperature. Although we could not conclude definitely that serum TNF levels correlated with severity of GVHD, it was suggested that TNF may be produced as a result of latent infections or immunological reaction against non-HLA allogeneic antigens.

[Intracerebral myeloblastoma developed in a patient with acute monocytic leukemia associated with inv (16) (p13q22)].

A 26 year-old man was diagnosed as having acute monocytic leukemia (M5b: FAB classification) associated with inv (16) (p13q22). Remission induction therapy showed good results, but two years later, he complained visual blurring and revealed right papilledema. Lumbar puncture showed leukemic cell infiltration. Irradiation to the orbita, intrathecal injection of MTX and Ara-C, until the cerebrospinal fluid cleared of leukemic cells, and chemotherapy were performed. One month later, he also complained visual blurring and left papilledema was found. After whole brain irradiation, intrathecal injection and chemotherapy, papilledema disappeared. Then, one year later, paralysis of right lower extremity appeared and brain computed tomography (CT) demonstrated tumor with increased density in the left frontal lobe, which enhanced with contrast material. Analysis of spinal fluid demonstrated abnormal cells. He was treated radiation therapy combined with intrathecal MTX and Ara-C. The patient survives currently three years after diagnosis and remains free of central nervous system disease. Because the patients with inv (16) have a high incidence of CNS involvement, they should be monitored closely with periodic lumber punctures.

Masked Ph chromosome due to a new type of translocation in a patient with chronic myelogenous leukemia.

A chronic myelogenous leukemia patient with a masked Ph chromosome due to a new type of translocation, t(9;11;22)(q34;p11;q11), is reported.