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P Schulman

Publications and source records attributed to P Schulman.

At least 19 recordsLinked to original sources
PubMed2003

Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195.

HuM195 is a humanized, unconjugated, anti-CD33 monoclonal antibody. Fifty adult patients with relapsed or refractory AML were randomized to receive HuM195 at a dose of 12 or 36 mg/m(2) by intravenous infusion over 4 h on days 1-4 and 15-18. Patients with stable or responding disease received two additional cycles on days 29-32 and 43-46. HuM195 was given as first salvage therapy in 24 patients and as second or subsequent salvage therapy in 26 patients. Pretreatment blast percentage in the marrow was between 5 and 30% in 20 patients with the others having blast counts greater than 30%. The median age of patients was 62 years (range 26-86) and CD33 was detected in 95% of patients for whom immunophenotyping was available. Of 49 evaluable patients, two complete and one partial remission were observed. All three responses were in patients treated at the 12 mg/m(2) dose level and all had baseline blast percentages less than 30%. Decreases in blast counts ranging from 30 to 74% were seen in nine additional patients. Infusion-related events of fever and chills occurred in the majority of patients and were generally mild and primarily related to the first dose of antibody. No hepatic, renal or cardiac toxicities were observed and other adverse events such as nausea, vomiting, mucositis and diarrhea were uncommon or felt to be unrelated to HuM195. In addition, anti-HuM195 responses were not detected. HuM195 as a single agent has minimal, but observable, anti-leukemic activity in patients with relapsed or refractory AML and activity is confined to patients with low burden disease. No significant differences in clinical efficacy or toxicity were seen between the two dose levels of antibody. HuM195 was well tolerated with infusion-related fevers and chills the predominant toxicities seen. Meaningful clinical efficacy of this unconjugated monoclonal antibody may be realized only in patients with minimal residual disease, or in combination with chemotherapy.

Adult↗
PubMed2001

Treatment of aggressive non-Hodgkin's lymphoma in elderly patients with thiotepa, Novantrone (mitoxantrone), vincristine, prednisone (TNOP).

The aging of the population and the increased incidence of non-Hodgkin's lymphoma will result in a large number of elderly patients with this disorder. Newer therapies will be required for this group of patients. This article reports a new therapy for elderly patients with diffuse aggressive non-Hodgkin's lymphoma. Patients were treated with TNOP (thiotepa 20 mg/m(2), mitoxantrone (Novantrone) 10 mg/m(2), vincristine (Oncovin) 1 mg/m(2) all on day 1 and prednisone 60 mg/m(2) on days 1 through 5 of a 21-day course. Twenty-six patients were enrolled on study. The patients' ages ranged from 66 years to 87 years, with a mean age of 75.5 years. Eleven patients had a partial response (42%) and 4 patients had a complete response (15%) for a total response of 57%. Eighty-one percent of patients survived 1 year and 54% survived for 2 years. The median survival was 26 months. Hematologic and nonhematologic toxicity was tolerable. We believe that TNOP is an excellent therapeutic option in this group of elderly patients, particularly in the palliative setting.

Aged↗
PubMed2000

Congenital unilateral hydrocephalus--CT findings.

Congenital unilateral hydrocephalus is extremely uncommon with 18 cases previously reported in the English literature. Two additional newborns with unilateral hydrocephalus are presented. The second baby also presented a mega cisterna magna. This unusual association between Dandy-Walker variant and unilateral hydrocephalus has not been previously reported. Following ventriculo-peritoneal shunt, the babies had a normal cognitive neurodevelopment. The role of cranial computed tomography (CT) in diagnosis and follow-up is emphasized.

Brain↗
PubMed1999

Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia.

Cellular immunophenotypic studies were performed on a cohort of randomly selected IgM(+) B-chronic lymphocytic leukemia (B-CLL) cases for which Ig V(H) and V(L) gene sequences were available. The cases were categorized based on V gene mutation status and CD38 expression and analyzed for treatment history and survival. The B-CLL cases could be divided into 2 groups. Those patients with unmutated V genes displayed higher percentages of CD38(+) B-CLL cells (>/=30%) than those with mutated V genes that had lower percentages of CD38(+) cells (<30%). Patients in both the unmutated and the >/=30% CD38(+) groups responded poorly to continuous multiregimen chemotherapy (including fludarabine) and had shorter survival. In contrast, the mutated and the <30% CD38(+) groups required minimal or no chemotherapy and had prolonged survival. These observations were true also for those patients who stratified to the Rai intermediate risk category. In the mutated and the <30% CD38(+) groups, males and females were virtually equally distributed, whereas in the unmutated and the >/=30% CD38(+) groups, a marked male predominance was found. Thus, Ig V gene mutation status and the percentages of CD38(+) B-CLL cells appear to be accurate predictors of clinical outcome in B-CLL patients. These parameters, especially CD38 expression that can be analyzed conveniently in most clinical laboratories, should be valuable adjuncts to the present staging systems for predicting the clinical course in individual B-CLL cases. Future evaluations of new therapeutic strategies and drugs should take into account the different natural histories of patients categorized in these manners.

Antigens, CD↗
PubMed1998

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the VH genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.

Amino Acid Sequence↗
PubMed1998

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111.

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.

Adolescent↗
PubMed1997

Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic lymphocytic leukemia.

The role of T cells in chronic lymphocytic leukemia (CLL) has not been extensively investigated, since the most prominent cellular abnormality in CLL involves the clonal expansion of B cells. In this study we have undertaken a comprehensive analysis of the CD4+ and CD8+ T cell repertoire in a population of CLL patients (n = 19) and age-matched controls (n = 22). The TCR repertoire analysis was performed using a multiplex PCR assay for CDR3 length, an approach that allows for the detection of underlying oligoclonality in complex T cell populations. We established that oligoclonality was substantially more frequent in both the CD4+ and CD8+ T cell populations of CLL patients than in the age-matched controls (p < 0.001). Using three-color FACS analysis with a panel of TCRV segment-specific mAbs, we also established that oligoclonal expansions are predominantly found in the CD57+ subset of both the CD4+ and CD8+ T cell populations. The frequency of the CD57 marker on CD4+ T cells was increased in the setting of CLL (% CD57 = 14.8 +/- 13.0%) compared with that in normal controls (% CD57 = 3.3 +/- 3.0%; p < 0.001). An elevated frequency of CD4+CD57+ T cells was correlated with more advanced disease. Similarly, the most extreme oligoclonal expansions of CD4+CD57+ T cells occurred in CLL patients who had progressed beyond Rai stage 0. These data document profound alterations in the T cell repertoire of CLL patients and point to a role for clonal T cell populations in the pathogenesis of this disease.

Adult↗
PubMed1997

A double-blind, randomized study of two different dosage regimens of intravenous dolasetron in patients receiving high-dose cisplatin chemotherapy.

This study compared the antiemetic efficacy and safety of two different intravenous (i.v.) dolasetron dosing regimens in patients receiving their first course of high-dose (> or = 80 mg/m2) cisplatin. Of 30 patients enrolled, 14 received a single i.v. dolasetron dose (0.6 mg/kg) before cisplatin and 16 received a multiple i.v. dose regimen (0.6 mg/kg x 3) given before and after cisplatin. Complete plus major responses were achieved by 71% (10/14) of patients who received single-dose dolasetron and by 50% (8/16) of those who received the multiple-dose regimen. Forty-three percent (6/14) of patients who received the single dose had a complete response compared with 25% (4/16) who received multiple doses. Multiple doses resulted in less nausea at 24 hr following cisplatin; however, differences were not statistically significant. Both regimens were well tolerated, with mild headache (33%) and diarrhea (13%) the most common adverse events. This study demonstrated that a single 0.6-mg/kg dose of dolasetron given before chemotherapy provides equivalent antiemetic efficacy to three 0.6-mg/kg doses given before and after high-dose cisplatin chemotherapy; thus, there was no additional antiemetic benefit by using the multiple-dose regimen.

Aged↗
PubMed1996

Examples of in vivo isotype class switching in IgM+ chronic lymphocytic leukemia B cells.

Chronic lymphocytic leukemia (CLL) usually involves the expansion of a clone of CD5+ B cells synthesizing IgM antibodies. These B cells appear to be blocked at the antigen receptor-expressing stage of B cell differentiation and are thought not to undergo an isotype class switch to IgG or IgA production. In vivo and in vitro studies suggest, however, that in some instances terminal differentiation and isotype switching can occur. To test the hypothesis that in vivo isotype class switching occurs in IgM+ B-type CLL cells, we analyzed the PBMC of 19 CLL patients for the presence of transcripts encoding the rearranged CLL V(H)DJ(H) associated with either gamma or alpha H chains. The molecular data indicate that approximately 50% of B-CLL patients have amplifications of IgM+ B cells that undergo an isotype class switch. Switching to IgA appears to occur more often than to IgG; also, switching can involve different IgG subclasses in individual patients. In many instances, these CLL-related gamma and alpha transcripts are much more plentiful than those of normal B cells that produce the same isotype. These switched transcripts do not reveal evidence for the accumulation of significant numbers of new V(H) gene mutations. The cellular data indicate that B cells with lesser amounts of surface membrane IgD and higher IgM/IgD ratios are more likely to undergo this switching process. Furthermore, B cells expressing IgG and IgA of the same idiotype or V(H) family and the same CDR3 length as those of the CLL IgM+ clone can be identified in the blood of patients studied using multiparameter immunofluorescence analyses. Collectively, these data suggest that not all members of a B-CLL clone are frozen at the surface membrane Ig-expressing stage of B cell maturation, and that some members can switch to the production of non-IgM isotypes. The occurrence of switching without the accumulation of V gene mutations indicates that the processes of differentiation and diversification are not linked.

Adult↗
PubMed1996

Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11.

Gains of a single chromosome are frequent cytogenic findings in human cancer, but no molecular rearrangement has been consistently associated with any trisomy. In acute myeloid leukemia (AML), trisomy 11 (+11) occurring as a sole abnormality is the third most common trisomy. We have shown that the ALL1 gene, located at 11q23, can be rearranged as a result of a partial tandem duplication in two such cases of AML. To test the hypothesis that the partial tandem duplication of ALL1 is the recurrent molecular defect in cases of AML presenting with +11 as a sole cytogenic abnormality, we performed Southern analysis and PCR for defects of ALL1 in 17 cases of AML and one case of myelodysplastic syndrome with +11 or +11q but without cytogenic evidence of a structural abnormality involving 11q23. Twelve cases (67%) had rearrangement of ALL1, including 10 of 11 patients (91%) with +11 as a sole abnormality and 2 of 7 cases (29%) with +11 and other aberrations; all were classified as FAB M1 or M2. In 10 of the 12 cases, material was available for additional characterization; a partial tandem duplication of ALL1 was detected in each of these 10 cases (100%). Four cases demonstrated previously unreported duplications, two of which were detectable only by reverse transcription-PCR. Four patients with the ALL1 duplication also displayed a loss of material from 7q, suggesting an association between these two findings. We conclude that the partial tandem duplication of ALL1 is present in most, if not all, cases of AML with +11 as a sole abnormality, and can be found in cases of AML with +11 or +11q accompanied by other cytogenic abnormalities. The duplication is more prevalent in AML than was recognized previously in part because its size and location vary considerably, requiring a variety of molecular probes for detection. Our finding of the ALL1 duplication as a consistent defect in patients with +11 represents the first identification of a specific gene rearrangement associated with recurrent trisomy in human cancer.

Acute Disease↗
PubMed1996

Evidence for progenitors of chronic lymphocytic leukemia B cells that undergo intraclonal differentiation and diversification.

Peripheral blood mononuclear cells from five patients with IgG+ B-type chronic lymphocytic leukemia (B-CLL) were analyzed for the presence of clone-specific Ig H chain variable region gene mRNA transcripts linked to C mu and/or C alpha. This was assessed by (1) comparing the lengths of portions of the VHDJH of the IgG+ CLL clones with those of the mu and alpha isotype-expressing B cells, (2) performing clone-specific endonuclease digestion studies, and (3) determining the DNA sequences of the mu and alpha isotype-expressing cDNA. Thus, when B-cell mRNA from these five patients were reverse transcribed with C gamma-specific primers and then amplified by polymerase chain reaction, dominant cDNA were found with lengths corresponding to those of the IgG+ CLL B cell. In addition, in four cases, cDNA of lengths identical to those of the CLL B cell were detected when mRNA was reverse transcribed and amplified using c mu- and/or C alpha-specific primers, strongly suggesting clonal relatedness. These CLL-related mu- and alpha-expressing cDNA were present in greater amounts that unrelated (non-CLL) mu- and alpha-expressing cDNA from normal B cells that used genes of the same VH family. When the sequences of these CLL-related C mu- and C alpha-expressing cDNA were compared with those of the IgG+ CLL clones, it was clear that they were derived from the same ancestral gene as the IgG-expressing CLL B cell, thus documenting their common origin. Finally, nucleotide point mutations were observed in the mu- and alpha-expressing cDNA of certain patients, indicating divergence with the CLL. These data suggest that IgM+ B cells, which are precursors of the leukemic B cells, exist in increased numbers in the blood of most patients with IgG+ B-CELL and that these cells may differentiate, accumulate V genes mutations, and undergo isotype switching in vivo. In addition, the data are consistent with a sequential-hit model for the evolution of CLL.

Base Sequence↗
PubMed1996

Clinical and morphological features of cases of trisomy 13 in acute non-lymphocytic leukemia.

Trisomy 13 has been infrequently reported as a primary non-random karyotypic change in myeloid leukemias. To elucidate its clinical significance we examined the clinical and hematological data in nine ANLL patients in whom we found this change, in a series of 175 cytogenetically abnormal ANLL patients. Morphologically, six of the patients were FAB-M1, two were FAB-M4 and one was FAB-M5. Bone marrow aspirates contained more than 90% blasts in eight of the patients. By immunophenotype, TdT was present in four of the patients, CD34 was present in four of five patients tested and CD5 was present in one of five patients tested. Blast cells in all patients expressed two or more myeloid surface antigens. These data suggest the proliferation of an immature myeloid cell in these patients. Complete remission was achieved in seven patients; however, remissions were short-lived. Eight patients expired between 1 and 13 months from diagnosis (median survival 5 months). Combining our findings with data in the published literature on trisomy 13 in ANLL, a larger data set consisting of 29 patients was established to determine better the clinical significance of this cytogenetic entity in ANLL. We found that this cytogenetic change has been reported in all subsets of FAB classification excepting M6 and M7. Median age at presentation was 60 years and no association with gender was noted. Median WBC was 29.5 x 10(9)/l, the majority of patients were thrombocytopenic (median platelet count 86 x 10(9)/l) and median survival was 5.2 months. This study associates trisomy 13 with malignant transformation of myeloid progenitor cells. These patients respond well to induction therapy, but relapse occurs quickly and the survival duration is poor.

Adult↗
PubMed1996

Phase I study of high-dose etoposide phosphate in man.

Etoposide is a widely used cytotoxic agent with a broad spectrum of activity in human malignancies. This agent has been incorporated into many transplant regimens although toxicity occurs because of its poor water solubility and toxic excipients. Etoposide phosphate, a water soluble prodrug of etoposide, has been studied at conventional dosages in man and shown to have advantages over the parent compound. We have extended our previous experience with this new agent to evaluate the levels needed in transplantation protocols. This phase I study of intravenous high-dose etoposide phosphate over 2 h on days 1 and 2 was designed to determine whether or not dose linearity between the amount of etoposide phosphate administered to patients and generation of etoposide in vivo as seen with conventional dosages of this agent would be present at transplant-dose levels. In addition, the toxicities of these dose levels with the short infusion schedule were defined. A conservative dose escalation scheme was chosen based upon prior knowledge of etoposide. Thirty-one patients (19 male, 12 female) with CALGB performance status 0-1 with a variety of solid tumors entered this study. The patients were treated with dose levels of etoposide phosphate given as the etoposide-equivalent doses of 250, 500, 750, 1000, 1200, 1400, and 1600 mg/m2/day in 250-400 ml of normal saline given as an intravenous infusion over 2 h on days 1 and 2 every 28 days. After the maximal tolerated dose level was determined on this schedule, additional patients received etoposide phosphate as a 4 h infusion on both days in an attempt to reduce toxicities. G-CSF (5 micrograms/kg/day) was administered subcutaneously to all patients from day 3 until the WBC > or = 10000/microliters. Nonhematologic toxicity was considered to be dose limiting. Serial plasma samples for pharmacokinetics were obtained from patients on day 1 of cycle 1. For the 2 h infusion, the maximum tolerated dose of etoposide phosphate was 1000 mg/m2/day x 2 with dose limiting mucositis. In the small number of patients studied, the maximum tolerated dose was reached for the 4 h infusion at 1400 mg/m2/day of drug, again due to mucositis. Other toxicities, despite the rapid infusion schedule, were modest with transient mild headache being most common. At the highest doses etoposide phosphate was efficiently and rapidly dephosphorylated to etoposide. Etoposide generated by dephosphorylation of etoposide phosphate had plasma disposition curves characteristic of etoposide administered parenterally. One partial response occurred in a patient with small cell lung cancer. Etoposide phosphate can be rapidly infused in modest fluid volumes at dosages required for transplantation protocols with minimal acute side-effects. On a 2 h schedule, mucositis becomes the dose limiting nonhematologic toxicity. Mucositis seems to correlate with peak dose levels of the drug rather than total drug administered. On a 4 h infusion schedule given sequentially for 2 days, the maximum tolerated dosage could be increased 40% compared to the 2 h schedule. The relative ease of administration and the rapid conversion of this prodrug into etoposide should make it useful in high-dose therapy settings.

Adult↗
PubMed1995

Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B.

BACKGROUND: Elderly patients with primary acute myelogenous leukemia (AML) are less likely to enter remission than younger adults, in part because of a higher mortality rate related to severe myelosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to shorten the duration of neutropenia and decrease infectious complications when administered after chemotherapy to patients with lymphomas and solid tumors. METHODS: We randomly assigned 388 patients 60 years of age or older who had newly diagnosed primary AML to receive placebo or GM-CSF (5 micrograms per kilogram of body weight per day intravenously over a period of six hours) in a double-blind manner, beginning the day after the completion of three days of daunorubicin (45 mg per square meter of body-surface area per day) and seven days of cytarabine (200 mg per square meter per day by continuous intravenous infusion). If leukemia cells persisted in the marrow three weeks after the initiation of chemotherapy, further daunorubicin (two days) and cytarabine (five days) were administered. GM-CSF or placebo was given daily until the neutrophil count was at least 1000 per cubic millimeter, there was evidence of the regrowth of leukemia, or severe toxic effects attributable to the study infusion occurred. Patients who had a complete remission were then randomly assigned to receive one of two intensification regimens. RESULTS: Of 388 patients (median age, 69 years), 193 were randomly assigned to receive GM-CSF and 195 to placebo. The rate of complete remission was 51 percent (95 percent confidence interval, 44 to 59 percent) among those assigned to GM-CSF and 54 percent (95 percent confidence interval, 47 to 61 percent) among those assigned to receive placebo (P = 0.61). The reasons for failure (early death, death during marrow hypoplasia, and persistent leukemia), the incidence of severe or lethal infection, and the incidence of the regrowth of leukemia (2 percent overall) were similar in the two groups. The median duration of neutropenia was slightly shorter (P = 0.02) in the patients who received GM-CSF (15 days) than in those who received placebo (17 days), but the clinical importance of this result was minimal because the growth factor failed to lower the treatment-related mortality rate or improve the rate of complete remission. CONCLUSIONS: GM-CSF, in the dose and schedule we used, does not stimulate the regrowth of leukemia, but it also does not decrease the severe myelosuppressive consequences of initial chemotherapy or improve the response rate in patients 60 years of age or older with primary AML. It should not be recommended for use in such patients.

Aged↗
PubMed1995

Acute agranular CD4-positive natural killer cell leukemia. Comprehensive clinicopathologic studies including virologic and in vitro culture with inducing agents.

BACKGROUND: A 63-year-old male presented with fever, a subcutaneous nodule, gingival hypertrophy, lacrimal gland enlargement, and no lymphadenopathy or hepatosplenomegaly, but had anemia, thrombocytopenia, and peripheral blood (PB) plus bone marrow (BM) involvement by leukemic cells. There was minimal response to multiagent chemotherapy and local radiotherapy, with a survival of 6.5 months from disease diagnosis. METHODS: The PB and/or BM leukemic cells were evaluated using electron microscopy (EM), immunohistochemistry, flow-cytometric immunophenotyping, cytochemistry, cytogenetics, Southern blot analysis for gene rearrangement and Epstein-Barr virus (EBV), polymerase chain reaction for EBV and human herpes virus-6 (HHV-6), and in vitro culturing with inducing agents. RESULTS: The leukemic cells were agranular and monocytoid, with a hairy cell-like bone marrow biopsy infiltrate. Myeloperoxidase (MPO) and alpha-naphthyl butyrate esterase staining was negative, and periodic acid-Schiff staining was positive by light microscopy. Electron microscopy showed MPO negativity and a lack of parallel tubular arrays. The immunophenotype was CD3-, CD56+, CD4+, CD8-, CD15+, TCR1-, and TCR2-, with germline immunoglobulin and T-cell receptor genes and an abnormal karyotype (44XY, 5q-, -13, 13q+, -15). No genomic material for EBV or HHV-6 was detected. Cell cultures with butyrate and N,N-hexamethylene bis-acetamide suggested the possible induction of tumor cells to express a T-cell immunophenotype. CONCLUSION: A case of clonal acute natural killer (NK) cell leukemia with an unusual morphology (agranular) and unique phenotype (CD3-, CD56+, CD4+, CD15+) is presented. Unlike as in other acute NK leukemias, EBV was negative; there was no evidence of HHV-6. The tumor cell, after culturing with differentiating agents, may have been induced to express a T-cell immunophenotype.

Acetamides↗