Human T-lymphotropic virus laboratory testing of maternal blood at time of cord blood donations and clinical implications.

BACKGROUND: In the United States, blood products are tested for infectious diseases including human T-lymphotropic virus (HTLV)-I/II. Positive results of maternal blood samples at the time of cord blood (CB) donation must be reported to mother and physician. Tests for HTLV have a high false-positive rate. This is problematic because there is no prenatal testing of the mother. STUDY DESIGN AND METHODS: This study involves 119,769 maternal blood samples at time of CB donation and evaluates positive results for HTLV in screening tests, supplemental immunoassays, and nucleic acid tests (NATs). Infectious disease markers (IDMs) and maternal health histories of HTLV-positive and -negative mothers were compared. RESULTS: Of 119,769 mothers donating CB, 545 tested positive with the screening test, 33 were positive with the supplemental tests, and two were positive with NAT. When indeterminate results were excluded from the supplemental test only six were positive. Eight of 34 mothers with positive or indeterminate supplemental test results had received intravenous immunoglobulin. There were no significant differences between HTLV-positive and -negative mothers with regard to the incidence of other IDMs. CONCLUSIONS: Testing maternal blood for HTLV is problematic for CB banks, obstetricians, and mothers because of the high false-positive rate. CB banks need rapid turnaround time and supplemental testing. If results on the latter are positive the obstetrician should be notified, educated, do follow-up testing, and counseling. Indeterminate results on supplemental tests are most likely false positives. We recommend that mothers with positive or indeterminate supplemental test results have follow-up NAT.

Renal sinus myelolipoma coexistent with renal pelvis papillary transitional cell carcinoma: a case report.

A unique case of renal sinus myelolipoma presenting as a mass coexistent with papillary transitional cell carcinoma is reported. The patient was a 64-year-old man with a history of bladder transitional cell carcinoma. He presented with gross hematuria and a filling defect in the renal pelvis on computed tomography scan. Pathological findings revealed an irregular myxoid fatty mass, in addition to high-grade papillary transitional cell carcinoma. The differential diagnosis included myxoid liposarcoma, myxoid variant of malignant fibrous histiocytoma (myxofibrosarcoma), and angiomyolipoma. Immunoperoxidase staining confirmed the presence of hematopoietic cells, whereas diagnostic histological and immunohistochemical features of liposarcoma, myxofibrosarcoma, and angiomyolipoma were absent. Myelolipoma and papillary transitional cell carcinoma appear to be unrelated coexistent entities in this case.

The clinical reliability of automated cerebrospinal fluid cell counts on the Beckman-Coulter LH750 and Iris iQ200.

Although automation has improved the accuracy and precision of blood cell counts and is more rapid and less labor-intensive, cerebrospinal fluid (CSF) samples are still counted manually. We compared the IRIS iQ200 Body Fluids Module (Iris Diagnostics, Chatsworth, CA) and the Beckman-Coulter LH750 (Beckman-Coulter, Brea, CA) with manual counts and evaluated the impact of automation on the laboratory if clinically acceptable performance was to be maintained. Automated counts were compared with manual counts on 313 specimens. Clinical reliability was estimated using the weighted kappa coefficient and the impact of errors discussed in the context of a historic census of 3,653 samples spanning 19 months. Nucleated cell counts had a reliability of 0.73 for the LH750 and 0.84 for the iQ200. However, our results showed unacceptable rates of error at counts less than 200/microL (200 x 106/L) for the LH750 and less than 50/microL (50 x 106/L) for the iQ200, representing 94% and 83% of the census specimens, respectively. If clinical reliability is to be maintained, neither the LH750 nor iQ200 would have a significant impact on improving the efficiency of the laboratory because of the high percentage of low CSF cell counts.

Synchronous development of acute myeloid leukemia in recipient and donor after allogeneic bone marrow transplantation: report of a case with comments on donor evaluation.

BACKGROUND: A case of donor cell leukemia (DCL) is reported. A 42-year-old female developed acute myeloid leukemia (AML) of donor cell origin 18 months after a bone marrow transplant (BMT) from her brother. At the time DCL presented, the donor-brother was also diagnosed with AML showing identical cytogenetic abnormalities. The classification of DCL and recommendations for laboratory testing of potential hematopoietic stem cell (HSC) donors are discussed. STUDY DESIGN AND METHODS: Marrow specimens were obtained from the posterior iliac crest and analyzed using standard techniques. Leukemic cells were analyzed by flow cytometry. Karyotyping and fluorescence in situ hybridization were performed using standard methods. RESULTS: The recipient-sister's original diagnosis was erythroleukemia. Chromosome analysis showed a 46,XX,t(3;5)(q25;q34) karyotype. Both the recipient's new AML and the donor's AML showed an identical karyotype: 46,XY,inv(3)(q21q26),-7. Both patients were resistant to therapy and died. CONCLUSION: The clinical and biological aspects of DCL are discussed including the distinction between transformation of healthy donor cells to leukemic cells and transmission of preformed leukemic cells. The former represents almost all the reported cases of DCL compared with transmission of leukemic cells from donor to recipient. With an aging donor population, it is estimated that the latter will increase. Increased testing of older donors to include routine morphologic study of blood and marrow, cytogenetic studies, and evaluation for clonal lymphoproliferative disorders is recommended.

Effect of hydroxyurea on immature reticulocyte fraction in sickle cell anemia.

Immature reticulocyte fraction (IRF) is a good indicator of bone marrow erythropoiesis in response to hemolysis or tissue hypoxia and is markedly increased in sickle cell disease (SS). We compared IRF changes in SS patients with those who were treated with hydroxyurea (SS-HU), and those who had concurrent alpha globin gene deletion (SS-(- deletion). Forty-two patients including 16 SS, 16 SS-HU, and 10 SS-alpha-deletion patients were studied. Significant decreases (P <.01) in reticulocyte indices including IRF, the reticulocyte percentage, and absolute reticulocyte count (ARC) were observed in SS-alpha-deletion compared to SS patients. On the other hand, although the reticulocyte percentage (P <.01) and ARC (P <.01) were significantly decreased in SS-HU compared with SS patients, the IRF was persistently elevated in both groups (P = .4), suggesting continuous bone marrow stimulation in SS-HU patients in response to tissue hypoxia. The possible underlying physiological mechanisms are discussed.

Florid histiocytic hemophagocytosis following therapy with long acting G-CSF (pegfilgrastim).

We describe a case of histiocytic hemophagocytosis and increase in blasts in the bone marrow after administration of long acting G-CSF (pegfilgrastim) in a 71-year-old man with underlying myelodysplasia. Pegfilgrastim was discontinued, with resolution of the hemophagocytosis and marked decrease in blasts from 30 to 5%. We postulate that pegfilgrastim provided a continuous stimulation of the monocyte/macrophage system, resulting in histiocytic hemophagocytosis. We recommend caution in defining indications for the use of long acting preparations of G-CSF.

Transfusion-acquired Trypanosoma cruzi infection.

BACKGROUND: A 3(1/2)-year-old girl with Stage 4 neuroblastoma received multiple blood components and was subsequently diagnosed with Chagas disease, which is caused by Trypanosoma cruzi. STUDY DESIGN AND METHODS: All blood donors of the units that were transfused were requested to return to the collection facility for a blood sample to be tested for antibodies to T. cruzi. RESULTS: One first-time donor was found to be positive for the presence of T. cruzi antibodies. This donor was originally from Bolivia and immigrated to the United States 17 years previously. She had not returned to her native country since her emigration. CONCLUSIONS: This is the seventh reported case of Chagas disease transmission by blood transfusion in the United States and Canada. Although this would not be expected to occur in New England, it did, and this case demonstrates the significance of the immune status of patients as it relates to transfusion-acquired infections, the impact of geographic mobility in disease transmission, and the need for a licensed screening test for Chagas disease for the US blood supply.

Dicentric (17;20)(p11.2;q11.2): an uncommon cytogenetic abnormality in myeloid malignancies.

We report on two patients with myeloid disorders and complex karyotypes including a dicentric chromosome, dic(17;20)(p11.2;q11.2), resulting in the loss of most of 17p and 20q. The presence of the centromeres of chromosomes 17 and 20 in the dic(17;20), as well as the loss of TP53, were confirmed by fluorescence in situ hybridization. Deletions of 17p and 20q are recurrent abnormalities in hematologic disorders, particularly myelodysplastic syndrome and acute myeloid leukemia). However, a dic(17;20) is an uncommon finding. According to the few reports in the literature, dic(17;20) is associated with an unfavorable prognosis. The key mechanism might be the loss of TP53 as well as other tumor suppressor genes in 20q that may have a critical role in tumor genesis.

Benign chronic neutropenia with abnormalities involving 16q22, affecting mother and daughter.

We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) x 10(9)/L with a median value of 1.02 x 10(9)/L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others.

Spurious dyserythropoiesis.

We documented the occurrence and severity of dyserythropoiesis as an artifact of storage in bone marrow aspirates collected in EDTA. Bone marrow samples were obtained from 7 patients without myelodysplasia. Specimens were stored at room (20 degrees C-24 degrees C) or refrigerated (1 degrees C-6 degrees C) temperature and examined for dyserythropoiesis at 0, 1, 2, and 3 days. Initial specimens showed few dyserythropoietic abnormalities; nuclear aberrations occurred in 1.07%+/-0.06% (mean +/- SEM) of the erythroid population. At room temperature, dyserythropoietic changes increased significantly with each day of storage. Nuclear and cytoplasmic alterations occurred; the former are diagnostically more important in the diagnosis of myelodysplastic syndromes. Cytoplasmic changes were more extensive than nuclear abnormalities. The mean +/- SEM percentage of erythroblasts with cytoplasmic vacuoles increased with each day of storage: day 0, 1.1%+/-0.2%; day 1, 22.1%+/-1.8%; day 2, 29.4%+/-2.0%; day 3, 35.6%+/-1.9%. Nuclear shape changes increased to 6.21%+/-1.12%, 11.36%+/-1.12%, and 12.85%+/-1.20% on days 1, 2, and 3, respectively. After 1 day of storage, sufficient dysplastic changes occur to cause difficulty in the diagnosis of a myelodysplastic syndrome. Changes are inhibited significantly by refrigerated storage.