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J Cuttner

Publications and source records attributed to J Cuttner.

At least 37 records · Page 2Linked to original sources
PubMed1987

Clinical importance of myeloid antigen expression in adult acute lymphoblastic leukemia.

To determine the clinical importance of immunophenotypes in adult acute lymphoblastic leukemia (ALL), we prospectively studied 76 patients with this condition. Before treatment, lymphoblasts were tested for reactivity with monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. Unexpectedly, myeloid antigens (MCS-2 or MY9) were identified in 25 patients (33 percent), usually in conjunction with B-cell or T-cell antigens. Among My+ patients, 15 (60 percent) expressed B-cell antigens (B+T-My+); all 6 tested had rearranged immunoglobulin genes. Five patients (20 percent) expressed T-cell antigens (B-T+My+), and one My+ patient expressed both B-cell and T-cell antigens. Only myeloid antigens (B-T-My+) were expressed in four patients (16 percent); three who were tested had germ-line immunoglobulin and T-cell-receptor gene configurations. Although no significant differences in presenting clinical features were found, My+ patients had fewer complete remissions than My- patients (35 vs. 76 percent, P less than 0.01). No differences in response or survival were observed between My+ and My- patients expressing T-cell antigens. However, among those expressing B-cell antigens, My+ patients had fewer complete remissions (29 vs. 71 percent, P = 0.02) and shorter survival (P = 0.03; median, 8.1 vs. greater than 26 months). These findings indicate that expression of myeloid antigen identifies a high-risk group of patients with adult ALL for whom alternative forms of treatment should be investigated.

Adult↗
PubMed1987

Iatrogenic and idiopathic acute myelogenous leukemia: a comparison of clinical features and treatment complications.

We have compared the clinical and laboratory features as well as treatment complications observed in 6 patients with iatrogenic acute myelogenous leukemia (I-AML) with those of 26 patients with idiopathic acute myelogenous leukemia (AML). I-AML patients were significantly younger and their disease appeared less virulent on admission than in the AML patients. Following identical chemotherapy, hemorrhagic complications and the need for platelet support were found to be similar for both groups. Major infections, including systemic candidiasis and Gram-negative septicemias, occurred 3 times more frequently among I-AML than AML patients. More marked suppression and delayed regeneration of the bone marrow also occurred in I-AML patients. These observations and other factors, such as post-splenectomy state and inherent immune deficiency among surgically staged lymphoma patients as well as radiation induced immunologic impairment, may have contributed to the increased propensity to develop infection observed in this group of patients. Five of the 6 I-AML and 17 of the 26 AML patients achieved remission. We attribute the satisfactory outcome in our I-AML patients to treatment in a protective environment and availability of facilities for hematologic supportive care.

Adult↗
PubMed1987

Treatment of acute myeloid leukemia cells in vitro with a monoclonal antibody recognizing a myeloid differentiation antigen allows normal progenitor cells to be expressed.

Monoclonal antibody L4F3 reacts with most acute myeloid leukemia (AML) cells and virtually all normal granulocyte/monocyte colony-forming cells (CFU-GM). Our objective was to determine whether lysis of AML cells with L4F3 and complement allowed expression of normal myeloid progenitors. The five glucose-6-phosphate dehydrogenase (G6PD) heterozygous patients with AML studied manifested only a single G6PD type in blast cells and in most or all granulocyte colony-forming cells, indicating that the leukemias developed clonally. The cells remaining after L4F3 treatment from two of the patients gave rise to granulocytic colonies that expressed the G6PD type not seen in the leukemic clone, indicating that they were derived from normal progenitors (CFU-GM). L4F3-treated cells from these two patients cultured over an irradiated adherent cell layer from normal long-term marrow cultures also gave rise to CFU-GM, which were shown by G6PD analysis to be predominantly nonleukemic. In the other three patients, the progenitor cells remaining after L4F3 treatment were derived mainly from the leukemic clone. The data suggest that in vitro cytolytic treatment with L4F3 of cells from certain patients with AML can enable normal, presumably highly immature progenitors to be expressed.

Adolescent↗
PubMed1987

Mitoxantrone and ara-C in previously treated patients with acute myelogenous leukemia.

Mitoxantrone is a synthetic aminoanthraquinone we have previously reported to be effective for patients with acute leukemia in relapse. We presently report the results of a trial of mitoxantrone in combination with cytosine arabinoside (ara-C) in patients with refractory or relapsed acute myelocytic leukemia (AML). Forty-nine patients, 24 males and 25 females, with a median age of 56, of whom 32 were in first relapse, four were in second relapse, and 13 had primarily refractory AML, were treated with mitoxantrone 10 mg/m2 daily for 3 days and ara-C 100 mg/m2 daily by continuous infusion for 7 days. Twenty patients (62.5%) with first relapse AML achieved M1 marrow, whereas only two of 13 patients with refractory AML did; none of four patients with more than one prior remission responded. Marrow recovery was observed in a median of 32 days. Remissions were maintained with monthly ara-C plus mitoxantrone alternating with ara-C plus 6-TG; median duration of remission was 8 months and two patients are in continuing remission at 8 and 16 months. Treatment was well tolerated, with minimal nausea and vomiting, diarrhea, drug-induced mucositis. Treatment-related cardiac toxicity was not observed. Transient hepatic dysfunction was observed in greater than 50% of courses. Mitoxantrone plus ara-C is an active combination with great promise for the therapy of previously untreated patients with AML.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Clotrimazole treatment for prevention of oral candidiasis in patients with acute leukemia undergoing chemotherapy. Results of a double-blind study.

Fungal infections have become an increasing cause of morbidity in patients with acute leukemia undergoing chemotherapy. Oral candidiasis is prone to develop in these patients, and there is also a risk of the development of esophageal Candida infection. Clotrimazole troches have been previously reported to be effective in the treatment of documented oral Candida infection. This report documents a double-blind controlled study in 30 patients with acute leukemia in which the effectiveness of clotrimazole troches in preventing oropharyngeal candidiasis was assessed. Patients were randomly assigned to receive 10 mg troches of clotrimazole or a placebo three times per day. Mucosal scrapings were obtained weekly and examined directly by smear and culture. There were 28 evaluable patients. Of 12 patients with oral Candida infection, 11 were taking placebo and one received clotrimazole (p = 0.0002). Clotrimazole is effective in preventing oropharyngeal candidiasis.

Acute Disease↗
PubMed1986

The reproducibility of acute lymphoblastic leukemia phenotype determinations: evaluation of monoclonal antibody and conventional hematopoietic markers.

Peripheral blood and/or bone marrow lymphoblasts from 25 patients with acute lymphoblastic leukemia (ALL) were tested with a panel of monoclonal antibodies (MoAbs) and conventional hematopoietic markers by three different laboratories. The results were analysed to evaluate the reproducibility of ALL phenotype determinations. Specimens were transported between laboratories by 24-h courier service and were classified on the basis of indirect immunofluorescence MoAb reactivities as follows: B-lineage ALL (BA-1+T-MCS-2-); T-lineage ALL (T+BA-1-MCS-2-); myeloid antigen ALL (MCS-2+BA-1-CALLA-T-) and unclassified ALL (BA-1-MCS-2-CALLA-T-). Conventional marker studies for surface immunoglobulin (sIg), cytoplasmic immunoglobulin (cIg), sheep erythrocyte rosette formation (E) and nuclear terminal deoxynucleotidyl transferase (TdT) were also performed. In the cases with sufficient marker data to permit classification, 90% (18/20) were identically classified by different laboratories and this concordance was statistically significant (p less than 0.05). The agreement between laboratories for individual MoAb and conventional marker analyses was statistically significant (p less than 0.05) for all markers with the exception of BA-2, cIg and TdT determinations. Six of 7 discordant BA-2 cases represented BA-2+ evaluations which had subsequent BA-2- results following specimen transportation. These findings suggest instability of the BA-2 antigen to transport conditions. A similar pattern of positive to negative evaluations following transportation was observed in 5/5 discordant results involving other MoAbs. Disagreement between laboratories for cIg and TdT determinations implies that the detection of cytoplasmic or nuclear antigens may be more prone to subjective interpretation than cell surface antigen marker analyses. Our findings suggest that immunofluorescence marker studies employing MoAbs to cell surface antigens are in general highly reproducible. Our results also indicate that specimen storage conditions and the cellular location of target antigens are important variables which may affect the reproducibility of ALL phenotype determinations.

Antibodies, Monoclonal↗
PubMed1986

Trisomy 22--a new abnormality found in acute leukemia characterized by eosinophilia and monocytoid blasts expressing immature differentiation antigens.

Bone marrow cells from three patients with acute myeloid leukemia, with marrow eosinophilia and monocytoid blasts, showed a new nonrandom chromosomal abnormality, trisomy 22. In two patients the classification of leukemia was M4 and in the third patient M2 (FAB classification). Pretreatment bone marrows in these patients revealed 31%, 30%, and 4% eosinophils, respectively. Blast cells isolated from peripheral blood were Ia-positive and expressed immature monocyte lineage antigens (U26, U28, U48) in 26%-92% of cells. All three patients had a population of bone marrow cells characterized by an extra chromosome #22. One patient also had inversion of chromosome #16. Trisomy 22, bone marrow eosinophilia, and monocytoid blasts displaying early monocyte differentiation antigens may represent a new subgroup of patients with acute myeloid leukemia.

Adult↗
PubMed1986

Therapy of refractory adult acute lymphoblastic leukemia with vincristine and prednisone plus tandem methotrexate and L-asparaginase. Results of a Cancer and Leukemia Group B Study.

Methotrexate (MTX) and L-asparaginase (ASP) are effective agents in the treatment of acute lymphoblastic leukemia (ALL). The effects of combining MTX and ASP are schedule dependent. To investigate this schedule dependency, the Cancer and Leukemia Group B (CALGB) employed vincristine and prednisone with progressive dose escalation of moderate-dose MTX (125 mg/m2) followed 24 h later with ASP (6,000 U/m2) in refractory adult ALL. We treated 38 patients with refractory or first relapse adult ALL. Most patients had received prior ASP (92%) and MTX (72%). A complete remission was achieved in 25% with a median duration of remission of 21 weeks. The median survival for the entire group was 7.4 months. Therapy was well tolerated and toxicity was acceptable. Our response rate was lower than other tandem MTX and ASP adult ALL trials. Therapy was similar with other series, with the exception of the dose of ASP employed. We conclude that tandem MTX and ASP, in the doses and schedule used here, has only modest activity in previously treated adult ALL. This regimen offers little advantage to other salvage regimens.

Adult↗
PubMed1986

Pseudomonas maltophilia exoenzyme activity as correlate in pathogenesis of ecthyma gangrenosum.

Ecthyma gangrenosum has not been described during the course of blood stream invasion with Pseudomonas maltophilia, although it occurs with a 30% frequency in Pseudomonas aeruginosa septicemia. We isolated P. maltophilia from the blood and an ecthyma lesion in a leukemic patient. The organism was an avid protease and elastase producer and hence mimicked the exoenzyme profile of invasive P. aeruginosa. The patient responded to moxalactam to which the isolate was susceptible in vitro. On the basis of this report, P. maltophilia may be included among an emerging number of gram-negative bacillary species capable of producing severe cutaneous manifestations of bacteremia.

Aged↗
PubMed1985

Tartrate-resistant acid phosphatase staining of monocytes in Gaucher disease.

Cytochemical studies were performed on peripheral blood from 30 patients with type 1 Gaucher disease. In 29 of the patients, peripheral blood monocytes stained positively for tartrate-resistant acid phosphatase, whereas monocytes from 18 normal individuals and 14 patients with monocytosis did not. In the Gaucher patients, the percentage of monocyte positivity for tartrate-resistant acid phosphatase ranged from 2 to 97. There was no correlation between the percent monocyte staining and the degree of disease severity, as measured by hepatosplenomegaly, pancytopenia, or extent of bone disease, for the group as a whole. In Gaucher patients who had not undergone splenectomy, however, there was a significant correlation between percent monocyte staining and the degree of hepatosplenomegaly, anemia, and thrombocytopenia. The presence of tartrate-resistant acid phosphatase may be secondary to the lysosomal accumulation of glucosyl ceramide within these monocytes, although this remains to be confirmed. If so, these circulating cells may represent precursors of the Gaucher cells in tissues. Tartrate-resistant acid phosphatase staining of peripheral blood monocytes may be useful as a diagnostic marker for Gaucher type 1 disease and for further studies on the pathogenesis of the disease.

Acid Phosphatase↗
PubMed1985

Pulmonary leukostasis as the single worst prognostic factor in patients with acute myelocytic leukemia and hyperleukocytosis.

Patients with acute myelocytic leukemia and hyperleukocytosis have a poor prognosis due to vascular leukostasis and infiltration in the central nervous system and lungs. The clinical records of all patients with a new diagnosis of acute myelocytic leukemia and initial white blood cell count greater than 100,000 X 10(9)/liter admitted to the Mount Sinai Medical Center between the years 1974 and 1983 were examined. Forty-three patients were identified, 22 of whom had clinical and/or pathologic evidence of leukostasis of the central nervous system and/or lung. All patients received induction chemotherapy with daunorubicin and a continuous infusion of cytosine arabinoside. Thirty-five patients also underwent therapeutic leukapheresis prior to induction chemotherapy. The overall remission induction rate in these 43 patients was 51 percent. Fifteen patients had lung leukostasis; the remission rate for these patients was 27 percent (three complete remissions, one partial remission), as compared with a remission rate of 64 percent (18 of 28) for those without pulmonary leukostasis (chi 21 = 5.53; p = 0.02). Thirteen patients had central nervous system infiltration; the remission rate for these patients was 46 percent (five complete remissions, one partial remission), as compared with 53 percent (16 of 30) for patients without central nervous system involvement (chi 21 = 0.19; p = 0.67). The median survival of 21 patients without leukostasis was 10.8 months, as compared with 15.4 months for seven patients with central nervous system involvement and no lung leukostasis and 0.2 months for 15 patients with pulmonary leukostasis (chi 22 = 19.9; p less than 0.001). Thus, pulmonary leukostasis was found to be the single worst prognostic factor in this group of patients.

Adolescent↗
PubMed1985

Definition of a possible genetic basis for susceptibility to acute myelogenous leukemia associated with the presence of a polymorphic Ia epitope.

The polymorphic Ia epitope recognized by monoclonal antibody 109d6 is detectable on the leukemic cells of a significantly increased number of individuals with acute myelogenous leukemia, compared with its frequency in normal healthy control individuals. In control individuals, the presence of the 109d6 epitope is closely correlated with but not identical to the DRw53 allo-specificity. However, the frequency of particular conventional Ia allodeterminants, including DRw53, is not significantly elevated in the leukemia group. Considerable evidence supports the conclusion that the high frequency of the 109d6 epitope reflects an inherited basis for susceptibility to the development of acute myelogenous leukemia and not a differentiation event occurring in the leukemic lineage. The 109d6 determinant is expressed by leukemic myeloblasts as well as by homologous normal B cells and monocytes obtained from the same individuals during remission of the leukemia. Furthermore, in healthy family members the 109d6 epitope is encoded by Ia haplotypes that are shared with the patient. Of special interest, certain of these haplotypes have combinations of the 109d6 epitope and Ia specificities not commonly seen in normal individuals; here, also, healthy family members share these haplotypes.

Antibodies, Monoclonal↗
PubMed1985

Adult acute lymphoblastic leukemia phenotypes defined by monoclonal antibodies.

Pretreatment peripheral blood and/or bone marrow blasts from 90 adults with acute lymphoblastic leukemia (ALL) were analyzed as part of a prospective treatment protocol study. Specimens were tested by immunofluorescence cytofluorometry for reactivity with the following monoclonal antibodies (MoAbs): BA-1 (B cell antigen); T101, OKT11 (pan-T cell antigens [T]); 3A1 (T cell antigen); MCS-2 (myeloid antigen); J5 common ALL antigen (CALLA); BA4 (Ia antigen [Ia]); BA-2 (lymphohematopoietic antigen). Four major phenotypic groups were identified: B lineage ALL (BA-1+T-) (64%), T lineage ALL (T+BA-1-MCS-2-) (13%), unclassified ALL (BA-1-MCS-2-CALLA-T-) (9%) and myeloid antigen ALL (MCS-2+CALLA-T-) (7%). An additional group of patients, miscellaneous ALL (7%), was comprised of cases with unusual marker profiles. In B lineage ALL, all cases tested were Ia+MCS-2-, and the vast majority were CALLA+ (84%). In T lineage ALL, 42% expressed CALLA or Ia positivity. In unclassified ALL, the predominant phenotype was Ia+BA-2+. In myeloid antigen ALL, two of four tested were 3A1+ and all cases evaluated were BA-1-. Patients with myeloid antigen ALL were older (median age, 66 years) than patients in the other groups. The T lineage ALL group had higher leukocyte counts (median WBCs, 183,000/microL) and an increased incidence of anterior mediastinal mass at presentation. All patients received identical induction therapy. In CALLA+B lineage ALL, 30 of 46 (65%) achieved a complete remission. While the number of patients evaluated was small, 9 of 9 CALLA-B-lineage ALL and only two of six myeloid antigen ALL cases responded with a complete remission. The data suggest that these MoAbs are useful in the characterization of adult ALL.

Adult↗
PubMed1984

Confirming evidence for the clonal development and stem cell origin of Philadelphia chromosome-negative chronic myelogenous leukemia.

A 74-year old woman with Ph1-negative chronic myelogenous leukemia (CML) and heterozygous for glucose-6-phosphate dehydrogenase (G6PD) was studied. Both A and B types of G6PD were found in skin. In contrast, white blood cells and platelets showed only a single G6PD type A. These results provide further evidence that Ph1-negative CML has a stem cell origin and develops clonally.

Aged↗
PubMed1984

Definition of AML susceptibility and classification using monoclonal antibodies.

Of 112 patients with acute leukemia 13 exhibited terminal deoxyribonucleotidyl transferase activity (TdT) with a cell phenotype characterized by the presence of early or mature monocyte differentiation antigens detected by monoclonal antibodies and elevated serum lysozyme. These cells were either unclassifiable by cytochemical analysis or fell into the M2 or M5 categories by the French-American-British classification. These leukemias appear to form a distinct nosologic entity representing a malignant transformation among early cells in the monocyte lineage. Among 60 patients with acute myelogenous leukemia 87% expressed the polymorphic Ia antigen detected by monoclonal antibody 109d6 compared to an incidence of 40.5% in the control population, relative risk 9.2. Evidence was obtained that this antigen was present in healthy family members and remission B-cells and monocytes of patients, and that its presence was associated with a genetically defined susceptibility state for the development of acute myelogenous leukemia.

Antibodies, Monoclonal↗
PubMed1984

Clotrimazole treatment of oral candidiasis in patients with neoplastic disease.

A double-blind controlled study was performed to evaluate the effectiveness of clotrimazole in the treatment of oral candidiasis in patients with neoplastic disease. Six of seven patients who received clotrimazole had resolution of symptoms and signs of oral candidiasis. In five of six patients who received placebo, clinical progression of signs and symptoms occurred, esophagitis developed, and amphotericin B therapy had to be given. No toxicity was observed that could be attributed to clotrimazole. The results were statistically significant (p = 0.025 by Fisher's exact test). Clotrimazole is effective therapy for oral candidiasis in patients with neoplastic disease, and may prevent the development of esophagitis.

Candidiasis, Oral↗