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M J Borowitz

Publications and source records attributed to M J Borowitz.

At least 55 records · Page 3Linked to original sources
PubMed1996

Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias.

Normal expression of the hematopoietic growth factor receptor FLT3 (STK-1@Flk2) is limited to CD34+ stem/progenitor cells. We have evaluated the expression of FLT3 by RNase protection assay and Western blotting in 161 primary bone marrow (BM) samples from patients with leukemia. FLT3 RNA was found to be expressed at a higher level than in normal BM controls in 33 of 33 B-lineage acute leukemias, 11 of 12 acute myeloid leukemias (AMLs), and 3 of 11 T-cell acute leukemias (T-ALLs). Expression of FLT3 RNA was also observed in some cases of blast crisis CML. The FLT3 signal resulted from expression on the leukemic blasts, and was not caused by increased FLT3 expression on normal CD34+ stem/progenitor cells in the leukemic samples. To determine if FLT3 protein was also overexpressed, proteins were extracted from leukemic BM samples and screened by Western blotting with anti-FLT3 antisera. FLT3 protein was not detected in normal BM controls, but was found in 14 of 14 B-lineage ALLs, 36 of 41 AMLs, and 1 of 4 T-ALLs. Stimulation of patient samples with FLT3 ligand resulted in autophosphorylation of the FLT3 receptor, suggesting the receptor is functional in these cells. These data show that FLT3 RNA and protein are aberrantly expressed by AML and ALL cells in that CD34 expression and FLT3 expression are no longer synchronous, and suggest the possibility that overexpression of FLT3 could play a role in the survival and/or proliferation of malignant clones in acute myeloid and lymphoid leukemias.

Antigens, CD34↗
PubMed1996

Atypical clonal T-cell proliferation in infectious mononucleosis.

An atypical case of infectious mononucleosis characterized by fever, acute tonsillitis, and bilateral cervical adenopathy is reported in a previously healthy young man. Although serology was positive for the Epstein-Barr virus, the patient did not display peripheral blood lymphocytosis or atypical, reactive lymphocytes. The patient's tonsilar tissue revealed an expanded T-zone of diffuse, monomorphous lymphocytes suggestive of lymphoma. Immunophenotypic analysis of the tonsilar tissue demonstrated more than 90% expression of pan-T markers, while pan-B markers were positive in 5-10% of the interfollicular T-zone cells and in 90% of germinal centre cells. In situ hybridization with a probe specific for EBER1 demonstrated positive staining in approximately 1% of the interfollicular tonsilar lymphocytes. Finally, Southern blot analysis of tonsilar tissue demonstrated a clonal rearrangement of the T-cell receptor gene. The patient recovered from his infection and remains in good health years after presenting with his illness. This case illustrates that T-cell clonality must be evaluated with caution in the setting of a viral infection and can occur in association with benign, self-limited infectious mononucleosis.

Adult↗
PubMed1996

Multiparameter flow-cytometric analysis of bcl-2 and Fas expression in normal and neoplastic hematopoiesis.

Apoptosis (programmed cell death) is an important regulatory mechanism in hematopoiesis, and is thought to be a principal mechanism of action of cytotoxic chemotherapy. Proteins that modulate apoptosis include bcl-2, which inhibits apoptosis, and Fas (CD95, also known as APO-1), which induces apoptosis in susceptible cells bound by Fas ligand (FasL). To characterize precisely the expression of these apoptosis-regulatory proteins in normal and neoplastic hematopoiesis, the authors have performed multiparameter flow cytometric (FCM) analysis in a series of normal and abnormal marrow specimens. Among normal hematopoietic elements, bcl-2 expression was highest in myeloblasts (29 [+/- 9] x 10(3) molecules of equivalent soluble fluorochrome [MESF]), and lymphocytes (28[+/- 7] x 10(3) MESF). bcl-2 was essentially undetectable in granulocytes and nucleated red blood cells, whereas monocytes and B-cell precursors expressed intermediate levels of bcl-2 (11[+/- 4] x 10(3) and 7[+/- 1] x 10(3) MESF, respectively). Fas expression increased with granulocytic and monocytic differentiation; myeloblasts expressed 8(+/- 2) x 10(3) MESF, whereas granulocytes (15 [+/- 2] x 10(3) MESF) and monocytes (28[+/- 5] x 10(3) MESF) displayed relatively greater intensity of staining for Fas. Among lymphoid cells, Fas expression was heterogeneous. B cells expressed lower intensity Fas staining than both CD4+ and CD8+ T cells. Myeloblasts in 30 cases of myeloid leukemia and myelodysplasia studied for bcl-2 and/or Fas expression manifested variable levels of these molecules (range 9-105 x 10(3) MESF for bcl-2 and 3-33 x 10(3) MESF for Fas). In addition, intraclonal heterogeneity of bcl-2 and Fas expression was seen in certain cases of AML, which correlated with extent of differentiation. Among 28 cases of B-precursor ALL studied for bcl-2 and/or Fas expression, bcl-2 ranged from 22 to 60 x 10(3) MESF (P < .001 versus normal marrow B-cell precursors), and Fas varied between essentially undetectable levels and 6 x 10(3) MESF. In summary, normal marrow subsets display characteristic levels of the apoptosis-regulatory molecules, bcl-2 and Fas. In hematopoietic neoplasms, expression of bcl-2 and Fas varies among cases, and in some instances, within leukemic blast populations. Further study is required to understand the potential significance of this heterogeneous expression of bcl-2 and Fas in hematologic neoplasia.

Apoptosis↗
PubMed1996

Changes in red blood cell methotrexate pharmacology and their impact on outcome when cytarabine is infused with methotrexate in the treatment of acute lymphocytic leukemia in children: a pediatric oncology group study.

Since it is unclear whether methotrexate and cytarabine are synergistic or antagonistic in the treatment of acute lymphoblastic leukemia, the Pediatric Oncology Group studied the prognostic significance of a potential interaction between these agents. RBC methotrexate concentrations were compared from 140 patients at lower risk of relapse randomized to two treatment groups: one receiving six methotrexate infusions with overlapping cytarabine; the other, six methotrexate infusions alone. Samples from 248 patients from all risk groups were studied to determine whether patients with extremely low RBC methotrexate concentrations had inferior outcomes. Among low-risk patients studied 3 weeks after the sixth infusion, median RBC methotrexate concentrations were 0.13 nmol/ml RBCs (n = 71) for the methotrexate-only group and 0.02 nmol/ml RBCs (n = 69) for the methotrexate/cytarabine-treated low-risk patients, P < 0.001 by the two-sided Wilcoxon test. For low- and high-risk patients receiving methotrexate/cytarabine infusions, event-free survival at 1 and 3 years after RBC sampling was 97 +/- 2% and 90 +/- 3% for patients with concentrations greater than the median, and 88 +/- 3% and 78 +/- 4% for those with concentrations at or below the median. Log rank comparisons of event-free survival in the first year and overall yielded P = 0.005 and P = 0.04, respectively. Cytarabine altered methotrexate pharmacology when the drugs were infused together. Patients whose levels were extremely low had an adverse prognosis. Although this study could not assess efficacy of the methotrexate/cytarabine combination, it appears that concurrent administration is not optimal.

Adolescent↗
PubMed1995

Neutrophil-rich, Ki-1-positive anaplastic large-cell malignant lymphoma.

The presence of neutrophils, in the absence of necrosis, is uncommon in malignant lymphoma (ML). We identified a subgroup of Ki-1-positive anaplastic large cell ML (Ki-1 ALCL) in which neutrophils were a prominent component. Six of 20 cases of Ki-1 ALCL had a significant neutrophil infiltrate that varied from 5 to 10% to > 50% of cells per high power field. Neutrophils were not seen in 100 cases of other types of ML reviewed. Patients were first seen with skin lesions (four), localized lymphadenopathy (three), generalized lymphadenopathy (one), and localized extranodal disease (one). All had primary disease. Two patients had peripheral neutrophilia. Three of six patients had clinical stage IV disease. Four patients are currently in clinical remission; one died of recurrent disease; and one patient with acquired immunodeficiency syndrome (AIDS) died of Pneumocystis carinii pneumonia. Four cases demonstrated a T-cell phenotype, one of which arose in a patient with AIDS. Two had a B-cell phenotype. All cases were positive for CD30 (Ki-1). These observations expand the morphologic spectrum of Ki-1 ALCL to include a neutrophil-rich variant. We conclude that the presence of neutrophils is another morphologic feature shared by some cases of Ki-1 ALCL, lymphomatoid papulosis, and Hodgkin's disease, which suggests a possible pathogenetic link among them.

Adult↗
PubMed1994

Detection of terminal deoxynucleotidyl transferase by flow cytometry: a three color method.

This short communication describes a three-color flow cytometric analysis procedure for terminal deoxynucleotidyl transferase (TdT). The method combines CD45-gating principles and a new permeabilization method based on a commercially prepared lysing reagent. While traditional permeabilizing fixatives are often cumbersome to use, distort cell light scatter, and fail to retain the fluorochrome peridin chlorophyll alpha protein (perCP), this simple method retains light scatter and does not affect perCP, making it ideal for three-color analysis. The procedure simply involves staining whole blood or bone marrow with CD45 perCP and an appropriate phycoerythrin (PE) conjugated monoclonal antibody (MoAb) and lysing with FACS lysing solution (Becton Dickinson, San Jose, CA). After washing the cells, fluorescein isothiocyanate (FITC) conjugated anti-TdT is added. The cells are washed, fixed with formaldehyde, and acquired on a flow cytometer compensated for three-color analysis. Display of CD45 perCP vs. right angle light scatter (RALS) allows identification of blasts. Dual color expression of anti-TdT FITC and a PE conjugated MoAb identifies TdT expression on blast populations defined by specific lineage associated antigens. This method is not only useful for TdT analysis but may also prove to be a valuable tool for looking at expression of other cytoplasmic antigens in combination with surface antigens on CD45-defined blast populations.

DNA Nucleotidylexotransferase↗
PubMed1994

Hepatosplenic T-cell lymphoma: an unusual case of a gamma delta T-cell lymphoma with a blast-like terminal transformation.

We describe a case of a middle-aged women who presented with anemia and mild hepatosplenomegaly and who was found to have an unusual peripheral T-cell lymphoma with only subtle morphologically abnormal but mature-appearing cells noted in the blood and bone marrow. Less than 2 years after diagnosis the patient presented with an increasing white blood cell count to 26 x 10(9)/L, and numerous blasts were noted in the periphery. Flow cytometry studies showed cells with an unusual T-cell phenotype expressing the gamma delta T-cell receptor and restricted expression of the V delta 1 but not the V delta 2 protein, indicating the clonal nature of the proliferation. A clonal T-cell receptor gene rearrangement was seen with a V delta 1 probe. The patient died and was found at autopsy to have extensive hepatic sinusoidal infiltration by abnormal cells. The histopathologic, immunophenotypic, and molecular findings are those of "hepatosplenic T-cell lymphoma." In spite of the striking morphologic change during the course of the patient's disease the same phenotype and clonal rearrangement were found both at initial diagnosis and during terminal phase, indicating that this change represented a blast-like transformation of the patient's original lymphoproliferative disorder.

Female↗
PubMed1994

Flow cytometric reticulocyte analysis. Multiinstitutional interlaboratory correlation study.

Reticulocyte analysis by flow cytometry offers precision and sensitivity greater than those of conventional morphologic methods and permits derivation of a reticulocyte maturity index. However, interlaboratory variability has not yet been reported. The authors analyzed 310 samples at eight sites using 11 instruments over a 4-month period to examine intermethod and interlaboratory variabilities. Stains included thiazole orange, ethidium bromide, and auramine O. Instruments included models by Coulter, Becton Dickinson, TOA Medical Electronics, and Ortho Diagnostics. The coefficient of variation (CV) among all sites and methods on these samples varied as a function of the reticulocyte percentage, ranging from a mean CV of 69% for samples with < .5% reticulocytes to 24.1% for those with > 2.5% reticulocytes. The best performance was observed with the TOA R-1000 dedicated reticulocyte analyzers, with a mean CV of 18.4% for samples with < .5% reticulocytes and 4.6% for samples with > 2.5% reticulocytes. The reticulocyte maturity index showed comparable intersite precision, with a mean CV of 16% for samples with > 2.5% reticulocytes with multipurpose flow cytometers and a mean CV of 7.3% with the TOA R-1000 instruments. Interclass correlations among all sites ranged from .79 to .99 for the reticulocyte counts and .41 to .88 for the reticulocyte maturity index. The authors conclude that flow cytometric reticulocyte analysis is more precise than manual reticulocyte analysis. With greater automation of this methodology, further interlaboratory standardization of reticulocyte counts and the reticulocyte maturity index can be achieved.

Adolescent↗
PubMed1993

Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602).

Of 1,036 children with newly diagnosed non-T, non-B acute lymphoblastic leukemia (ALL) and a demonstrated cytogenetic abnormality treated on the frontline Pediatric Oncology Group (POG) therapeutic trial 8602, there were 33 patients with trisomy 21 as the sole abnormality. Of these 33, 14 had Down syndrome (DS). Although the non-DS (NDS) trisomy 21 cases tended to be older than the DS cases, there were no other significant differences in clinicobiologic features nor in treatment outcomes between the DS and NDS groups, nor between the entire trisomy 21 group and the other chromosome abnormality group. Among NDS patients with +21 and one additional abnormality, +X, +16, -20, and structural abnormalities involving 6q or 12p were common findings. Kaplan-Meier event-free survival (EFS) curves showed a 4-year EFS of 80% (SE, 12%) in NDS trisomy 21 cases, 71% (SE, 22%) in DS cases with trisomy 21 as the sole abnormality, and 69% (SE, 2%) in cases with other chromosome abnormalities. Trisomy 21 as a sole acquired abnormality in NDS patients suggests a good prognosis.

Child, Preschool↗
PubMed1993

High glucocorticoid receptor content of leukemic blasts is a favorable prognostic factor in childhood acute lymphoblastic leukemia.

We have previously shown that the number of glucocorticoid receptors (GR) per cell in malignant lymphoblasts from children with newly diagnosed pre-B- and early pre-B-cell acute lymphoblastic leukemia (ALL) has a positive correlation with the probability of successful remission induction (Quddus et al, Cancer Res, 45:6482, 1985). We report now on the long-term outcome for these patients treated on a single protocol with 3 different treatment arms, all of which included glucocorticoid pulses during maintenance therapy. GR were quantitated in leukemic cells from 546 children with ALL at the time of diagnosis. Immunophenotyping studies were performed on all specimens. Prior studies showed that in pre-B- and early pre-B-cell ALL, successful remission induction was associated with a median GR number of 9,900 sites/cell, whereas induction failure was associated with a median receptor number of 4,800 sites/cell. Long-term follow-up of these patients shows an association between higher GR number and improved prognosis. The 5-year event-free survival of 61.0% (SE 2.8%) for patients whose leukemic cells had greater than 8,000 receptors/cell and 47.3% (SE 3.3%) for those with less than 8,000 receptors/cell is significantly different (P < .001). This difference remains significant when adjusted multivariately for blast immunophenotype and clinical risk factors (P < .001) or for treatment type (P < .001). We conclude that GR number greater than 8,000 sites/leukemic cell is a favorable prognostic marker for children with acute lymphocytic leukemia. This finding offers deeper insights into molecular mechanisms of anti-leukemia therapy and suggests that manipulation of steroid receptor number might augment the antitumor response, thus opening new avenues for basic and clinical research.

Adolescent↗
PubMed1993

Predictability of the t(1;19)(q23;p13) from surface antigen phenotype: implications for screening cases of childhood acute lymphoblastic leukemia for molecular analysis: a Pediatric Oncology Group study.

The t(1;19)(q23;p13) translocation occurs in approximately 5% of B-precursor acute lymphoblastic leukemias (ALLs) occurring in children. Its presence has been associated with a poor prognosis, which may be overcome with more intensive therapy. Although leukemic cells from cases of t(1;19)-ALL frequently express cytoplasmic mu heavy chains, their complete antigenic profile remains undefined. Among 697 consecutive cases of B-precursor ALL with complete phenotypic studies using a panel of monoclonal antibodies, 22 cases were found to carry the t(1;19). Twenty of 22 cases had an identical, complex phenotype characterized by homogeneous expression of CD19, CD10, and CD9; complete absence of CD34; and at least partial absence of CD20. Overall, this phenotype was seen in only 8.0% (56 of 697) of childhood B-precursor ALL. One of the two remaining t(1;19)-carrying cases conformed to this phenotype, but was lacking data for CD9. The other case differed by virtue of expression of CD34 and was also hyperdiploid with 55 chromosomes. Molecular studies showed E2A-PBX1 abnormalities in all examined cases (12 of 12) with the t(1;19), including the case lacking CD9 data. In contrast, no E2A-PBX1 abnormalities were detected in the sole t(1;19)-ALL with CD34 expression. Seventeen cases with the characteristic phenotype and uninformative cytogenetics were also molecularly analyzed and 5 of 17 (including 4 of 8 with unsatisfactory cytogenetics and 1 of 9 with a normal karyotype) contained E2A gene rearrangements and E2A-PBX1 fusion mRNAs. Our results show that all cases of t(1;19)-ALL with concomitant E2A-PBX1 fusion invariably express a characteristic but uncommon profile of surface antigens. These observations suggest that selective molecular analysis of a small subset of patients (those with uninformative cytogenetics and the characteristic phenotype) can identify a significant number of additional cases of ALL with E2A-PBX1 fusion that might benefit from more intensive therapy.

Antigens, CD↗
PubMed1993

Human t(1;19)(q23;p13) pre-B acute lymphoblastic leukemia in mice with severe combined immunodeficiency.

Severe combined immunodeficient (SCID) mice were injected intravenously with 5 x 10(6) primary bone marrow (BM) blasts from newly diagnosed patients with E2A-PBX1 fusion transcript positive t(1;19)(q23;p13) pre-B acute lymphoblastic leukemia (ALL). A marked variation existed in the pattern and extent of leukemic cell engraftment in SCID mice challenged with t(1;19) pre-B ALL blasts. Blasts from some patients caused disseminated leukemia that was detected by histopathology and/or flow cytometry, whereas blasts from other patients produced occult leukemia that was only detected by flow cytometry and/or polymerase-chain reaction. Notably, the ability of primary t(1;19) pre-B ALL blasts to cause disseminated leukemia in SCID mice was associated with poor prognosis. Six of six patients whose blasts caused disseminated leukemia in SCID mice relapsed at a median of 7.8 months (range: 5.7 to 25.2 months). In contrast, the remaining four patients whose blasts did not engraft or only partially engrafted remain in complete remission at 28 to 47 months. A new E2A-PBX-1 fusion transcript positive t(1;19) pre-B ALL cell line (designated LC1;19) with the composite immunophenotype CD7-CD10+CD19+CD45-HLA-DR+C mu+ was established by expanding BM blasts from a SCID mouse, which died of human t(1;19) ALL at 7 weeks after inoculation of primary leukemic blasts from a t(1;19) ALL patient. This cell line caused disseminated and invariably fatal leukemia when greater than 10(4) cells were injected intravenously into SCID mice. Total body irradiation followed by syngeneic BM transplantation (BMT) showed limited efficacy against LC1;19 leukemia in SCID mice. To our knowledge, this study is the first to (1) examine the in vivo growth of primary t(1;19) pre-B ALL blasts in SCID mice and (2) show that leukemic blasts from a majority of newly diagnosed t(1;19) pre-B ALL patients cause disseminated human leukemia in SCID mice. Our results indicate that t(1;19) pre-B ALL is biologically heterogeneous with regard to its in vivo growth pattern in SCID mice, a feature that may be predictive of prognosis. The described LC1;19 SCID mouse model may prove particularly useful for designing more effective treatment strategies against poor-prognosis t(1;19) ALL.

Animals↗
PubMed1993

Marrow B-cell precursors are increased in lymphomas or systemic diseases associated with B-cell dysfunction.

Marrow regeneration is known to be associated with an increase in immature B cells, including CD10+ cells. A similar phenotype has been seen in some children with unusual cytopenias. This article describes 21 adult patients not recovering from chemotherapy, who had increased CD10+ cells in their marrows. These cells had the relatively uniform scatter properties of small lymphocytes by flow cytometry, and by multiparameter analysis were found to have a distinct phenotype in that they were CD19+, lacked surface immunoglobulin, and heterogeneity expressed CD20. In two of three patients tested, some but not all of these early B cells were TdT+. CD10+ cells accounted for 10-76% of total mononuclear cells. All 21 patients had some systemic illness. Thirteen patients had a diagnosis of lymphoma (three Hodgkin's, ten non-Hodgkin's); all ten of the latter were extranodal and seven of seven phenotyped cases were B-cell lymphomas. Seven patients had autoimmune disease (one also had lymphoma) and one had the acquired immunodeficiency syndrome with mycobacterial infection of the marrow. One patient with a history of a "viral illness" had a lymph node showing atypical lymphoid hyperplasia with progressive transformation of germinal centers. Examination of marrow core biopsies in these patients showed a proliferation of small lymphocytes ranging from a barely perceptible diffuse increase to numerous lymphoid aggregates. The extensive lymphocytosis seen in two marrows suggested a diagnosis of lymphoma on morphologic grounds alone, but neither these patients nor any others had B-cell clonal excess. The presence of this phenotype suggests nonspecific stimulation of marrow B-cell precursors associated with systemic B-cell activation in either an immunologic or neoplastic disorder. Presence of this unusual phenotype does not imply involvement of marrow by B-cell neoplasia.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Immunophenotyping of acute leukemia by flow cytometric analysis. Use of CD45 and right-angle light scatter to gate on leukemic blasts in three-color analysis.

This article describes a procedure for performing routine three-color flow cytometric analysis for acute leukemia on lysed whole bone marrow preparations. This technique uses the combination of CD45 intensity and right-angle light scatter (RALS) to distinguish leukemic cells from normal lymphocytes, monocytes, neutrophils, eosinophils, and nucleated red blood cells. On this display, leukemic cells occupy a unique blast region characterized by intermediate CD45 density and low RALS, which, in normal marrows, contains less than 5% of the total cells. This approach was applied to 39 cases of acute leukemia and 8 cases of myelodysplasia or myeloproliferative disorders. The estimate of blasts by flow cytometric analysis was correlated highly with morphologic leukemic cell counts over a wide range. Moreover, the pattern seen on the CD45-RALS display was different for different French-American-British subtypes of leukemia, suggesting that this pattern might be useful for categorization. When CD45-peridin chlorophyll alpha protein was combined with other pairs of fluorescein isothiocyanate- and phycoerythrin-conjugated reagents, it was possible to set an analysis window on the leukemic blasts and display dual-parameter (ie, green vs. red fluorescence) data regarding expression of two additional markers on the leukemic population. This gating strategy was superior to traditional forward-angle versus RALS displays in that it did a better job of isolating the leukemic cells analytically.

Bone Marrow↗
PubMed1993

Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide.

PURPOSE: To describe the occurrence of secondary acute myeloid leukemia (AML) in children with acute lymphoblastic leukemia (ALL) treated with etoposide (VP-16). PATIENTS AND METHODS: Two hundred five consecutive children with early B-lineage ALL were treated according to the Dallas/Fort Worth (DFW) protocol between January 1986 and July 1, 1991. Therapy included a four-drug induction followed by consolidation and continuation phases of nightly oral mercaptopurine (6-MP) and repetitive courses of divided-dose oral methotrexate (dMTX) and asparaginase (L-asp). Three doses of VP-16 and cytarabine (Ara-C) were given during consolidation and later, during continuation, two doses were given 3 to 4 days apart, every 9 weeks. Intrathecal (IT) chemotherapy was given throughout the treatment period. RESULTS: Two hundred three of the 205 patients entered remission. Only eight of these 203 children have had a bone marrow relapse (ALL). However, 10 other children have developed secondary AML 23 to 68 months following the diagnosis of ALL. Overall event-free survival (EFS) at 4 years is 79.3% +/- 5.1%, with a risk of secondary AML at 4 years of 5.9% +/- 3.2%. CONCLUSION: This experience provides strong evidence for a link between epipodophyllotoxin therapy and secondary AML since none of these children received alkylating agent therapy or irradiation. This serious complication raises concern as to the appropriate use of epipodophyllotoxins in the treatment of childhood ALL.

Acute Disease↗
PubMed1993

Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia.

PURPOSE: Immunophenotypes and karyotypes of leukemic cells were analyzed in a large series of Down syndrome patients with acute lymphoblastic leukemia (ALL) to examine the frequency of adverse prognostic features in comparison with other patients with ALL. PATIENTS AND METHODS: Presenting features and leukemic cell characteristics were compared for 76 patients with Down syndrome and 4,733 other patients with newly diagnosed ALL treated on protocols of the Pediatric Oncology Group (POG) and St Jude Children's Research Hospital (SJCRH). Treatment outcome was analyzed for the patients with non-T-cell disease enrolled on a single trial, for whom adequate follow-up data were available. RESULTS: Down syndrome patients had lower platelet counts (P < .01) and were less likely to have an anterior mediastinal mass (P < .01) or CNS leukemia (P = .01). They were significantly more likely to have the pre-B immunophenotype (49% v 25.5%, P < .01) and less likely to have T-cell ALL (5.5% v 16%, P = .01). There was a notable absence among patients with Down syndrome of the t(4;11), t(1;19), and t(9;22), which are chromosomal translocations associated with an adverse prognosis in ALL. Treatment outcome did not differ significantly between patients with Down syndrome and the other children with non-T-cell ALL (P = .21); a third of the treatment failures in the former group resulted from treatment-related toxicities. CONCLUSION: Children with Down syndrome and ALL had a low frequency of adverse clinicobiologic features at diagnosis. However, these findings did not translate into a superior outcome, apparently because of treatment-related toxicity in this group. Future trials should focus on pharmacokinetics and other strategies to reduce toxicity in these compromised patients.

Adolescent↗
PubMed1993

Abnormalities of circulating T-cell subpopulations in patients with cutaneous T-cell lymphoma: cutaneous lymphocyte-associated antigen expression on T cells correlates with extent of disease.

The recent characterization of the cutaneous lymphocyte-associated antigen (CLA) as a skin-selective homing receptor for skin-associated memory T cells has suggested a possible mechanism for the tropism demonstrated by the neoplastic T cells in cutaneous T-cell lymphoma (CTCL). In this study, we used five parameter flow cytometry to evaluate expression of CLA and the peripheral lymph node homing receptor L-selectin on circulating T cells in a series of patients with CTCL. Because CTCL cells were previously shown to be CD7-, we looked at expression of these receptors on the CD7- T-cell subset as well as on total T cells. Our results indicate that CTCL patients have increased levels of both CLA+ and CD7- cells in their peripheral blood and that these abnormalities are not seen in patients with other cutaneous disorders. The levels of the CLA-bearing subset correlated with extent of cutaneous but not lymph node disease. By contrast, the CD7- L-selectin+ subset correlated with peripheral lymph node involvement by CTCL. Only the CD7- L-selectin- subset correlated with the number of morphologically abnormal lymphocytes in the peripheral blood. The results support the hypothesis that expression of tissue-selective homing receptors contributes to the unique pattern of tissue involvement seen in patients with CTCL.

Antigens, CD↗