The relationship between serum erythropoietin (EP) and hemoglobin (Hb) concentrations was investigated in patients of iron deficiency anemia (IDA) in the course of iron replacement therapy to elucidate how the therapy induced changes in that relationship.
At first Hb-dependent EP levels were determined in 123 IDA patients prior to the treatment by the third-degree logarithmic regression of EP on the Hb deficit (d-Hb).
Following the start of iron supply, the deviation of observed EP values from the predicted level (EPc), i,e., δ-EP, was most obvious at the next phase of the onset of reticulocyte crisis; however, this deviation reduced with the alleviation of IDA. The value in maximum phase (δ-EPmx), as individually defined for each of 95 patients, correlated significantly with the severity of the pretreatment ID state (r=0.502, p<0.01). Partial correlation analysis revealed that about 80% of this gap was attributable to the ID state. Also, it was assumed that EP upregulation was twice that attributable to the Hb-deficit factor alone. The phase sequence of the δ-EP versus d-Hb relationship in 21 relapsed patients demonstrated a different rout from that observed in their improvement phase.
The ID state-induced upregulation of EP, i.e., EPc, was followed by a therapy-induced overshooting drop that was attributable to acute uptake of EP by shifted erythroid precursors. From the viewpoint of erythropoietic regulation, the subsequent down-regulation of EP in the mid to late phases was considered appropriate for the prevention of Hb over production.

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Malaria is relatively rare in Japan. Of 13 patients referred to our laboratory for malarial screening in the past 4 years, malarial parasties were detected in 8. Conventional screening procedures commonly detect hepatic dysfunction, thrombocytopenia, elevated LDH activity, and increased CRP levels in malaria patients. More notably, the 8 malaria patients identified by our laboratory also demonstrated reactive lymphocytosis. In the absence of additional clinical information, reactive lymphocytosis alone may be enough to warrant laboratory blood smear tests on the suspicion of malaria.
Conventional microscopic methods have often proved inconclusive in identifying malarial parasite species or detecting mixed infections. However, by combining the methods of DNA analysis with those of microscopy, we were able to conclusively diagnose all cases of suspected malaria.
As a test of their skills, 9 laboratory technicians relatively inexperienced with malarial parasites were asked to screen 6 samples: 3 containing malarial parasites, and 3 that were malaria-free. Although none of the technicians were able to accurately identify the samples without additional clinical information, 4 accurately identified all malarial samples when that information was provided. Experience is a crucial determinant of ability to detect malarial parasites by microscopic methods alone. Nonetheless, the findings of our study suggested the diagnostic accuracy of laboratory screening procedures for malaria can be significantly improved if combined with minimal clinical data and the techniques of DNA analysis.

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A 58-year-old man was admitted to our hospital in November 1992 because of fever and arthralgia. He was given a diagnosis of acute lymphoblastic leukemia and treated with an Ad-VP regimen, which resulted in complete remission. After two courses of consolidation therapy and intrathecal (IT) injections of methotrexate, Ara-C, and prednisolone the patient received high-dose Ara-C plus VP-16 followed by recombinant human G-CSF for the collection of peripheral blood stem cells. However, he relapsed with the appearance of leukemic cells in cerebrospinal fluid (CSF), and was accordingly given IT injections 8 more times.
After the disappearance of leukemic cells from CSF, the patient received a peripheral blood stem cell transplant (PBSCT) and achieved rapid hematopoietic recovery. However, he suffered mental aberrations and loss of consciousness 9 days after PBSCT.
Proton magnetic resonance spectroscopy (¹H-MRS) disclosed severe necrosis due to leukoence-phalopathy in the frontal lobe and invasion of leukemic cells around the lateral ventricles. The patient did not receive any therapy for neurological symptoms because of severe necrosis in the frontal lobe, and died of bone marrow relapse in April 1995. MRS is useful for the discrimination of leukoencephalopathy from leukemic cell invasion.

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Reverse transcriptase-polymerase chain reaction (RT-PCR) methods often detect the AML1/MTG8 fusion transcript even in acute myelogenous leukemia (AML) patients with t(8;21) who have been in long-term remission. We encountered 2 hypoplastic leukemia patients with t(8;21) who achieved cytogenetic remission with short-term conventional chemotherapy.
Patient 1 was a 42-year-old woman. Chromosomal analysis detected t(8;21)(q22;q22) and PCR analysis (35 cycles PCR amplification; detection limit 1×10^-5 cells) detected the AML1/MTG8 fusion transcript. Complete remission was obtained with 1 course of chemotherapy consisting of low-dose cytarabine (20 mg×14 days) and etoposide (50 mg×14 days). After 2 courses of consolidation chemotherapy consisting of conventional-dose cytarabine and mitoxantrone, the RT-PCR findings were negative for the AML1/MTG8 fusion transcript.
Patient 2 was a 67-year-old man. Cytogenetic analysis detected t(8;21)(q22;q22), and was positive for the AML1/MTG8 fusion transcript. After 2 courses of induction chemotherapy comprising low-dose cytarabine (20 mg×14 days) and etoposide (50 mg×14 days), and 3 courses of conventional consolidation chemotherapy, RT-PCR analysis confirmed the disappearance of the AML1/MTG8 fusion transcript.

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A 35-year-old pregnant woman had thrombocytopenia with a platelet count of 6.3×10⁴/μl. After her third normal delivery, peripheral blood studies revealed that the patient had a normal Hb concentration and leukocyte count, with mild thrombocytopenia. A diagnosis of idiopathic thrombocytopenic purpura (ITP) was made based on the high megakaryocyte count of 338/μl and PAIgG of 40.8 ng/10⁷ cells in January 1995. The patient was followed without treatment. She was 9 weeks pregnant on June 7, 1996, and desired an abortion. Her platelet count was 6.3×10⁴/μl, leukocyte count 8,600/μl, and Hb 13.7 g/dl at the time. She was given high-dose intravenous gammaglobulin (Globenin-I) at 400 mg/kg/day for 5 consecutive days. The platelet count was found to have decreased markedly, to 0.9×10⁴/μl on June 11. The percentage reduction in the Hb concentration, leukocyte count, and platelet count after gammaglobulin treatment was 11.7%, 46.6%, and 85.8%, respectively. The PAIgG titer had increased to 181.2 ng/10⁷ cells on June 17, but hypergammaglobulinemia was suspected. The patient was started on prednisolone on June 24, and an abortion was performed on July 29. The mechanism of thrombocytopenia after infusion of Globenin-I was unknown. We suspect that Globenin-I treated with polyethylene glycol was one of the possible causes of myelosuppression in this case.

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Neurological side effects and complications of cryoglobulinemia were observed during interferon-alpha (IFN-α) therapy in a patient with chronic myeloid leukemia (CML). A 50-year-old man was hospitalized because of leukocytosis and extramedullary tumors in the lumbar spine. In addition, the patient complained of dysesthesia in his feet. A diagnosis of accelerated phase CML was made. Administration of prednisolone, vincristine, hydroxyurea, and Ara-C and irradiation of the lumbar spine were started. Two manths later, the patients achieved hematologic response and the size of his tumors decreased. Thereafter, we started IFN-α treatment (3-6×10⁶ units daily) by intramuscular injection. After 8 weeks of this treatment, the patient complained of worsening dysesthesia in his feet. An axonal form of peripheral neuropathy was diagnosed by electrophysiological examination. Immunological studies revealed decreased complement levels and type III mixed cryoglobulinemia. Methylprednisolone pulse therapy alleviated the neurological symptoms and lowered the cryoglobulin levels. The clinical course suggested that mixed cryoglobulinemia was associated with CML and that the increase in cryoglobulin levels was caused by IFN-α and played a causative role in the worsening peripheral neuropathy. Therefore, to prevent these side effects, careful clinical assessment is necessary before starting IFN-α therapy.

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An 88-year-old Japanese woman with splenomegaly, but without lymphadenopathy, was admitted because of epigastric distress. Laboratory data disclosed an RBC of 310×10⁴/μl, Hb of 10.1 g/dl, Ht of 30.6%, Plt count of 9.8×10⁴/μl, and WBC of 4,470/μl with 38% abnormal lymphocytes. Peripheral blood films revealed lymphocytes with thin, short cytoplasmic villi, condensed nuclear chromatin, and small nucleoli. The lymphocytes stained negative for tartrate-resistant acid phosphatase. Also, immunophenotyping was positive for expression of the cell surface markers CD19, CD20, IgG, κ and HLA-DR, but not for CD5, CD10, CD11c, CD23, CD25, CD38, or CD103 antigens. Chromosomal analysis of peripheral blood cells disclosed the 46, XX, del(7), (q32) aberration. A splenectomy was performed simultaneously with partial colon resection because of a mucinous carcinoma found in the transverse colon. Histologic examination of resected spleen tissues revealed a distinctive pattern of white pulp infiltration by lymphoma cells. The histologic findings and clinical data were consistent with the features of splenic lymphoma with circulating villous lymphocytes. Our patient exhibited a relatively benign clinical course, and was being followed on an outpatient basis with no additional therapy.

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