Search PubMed⌕ Search

Biomedical subjects

D K Kalwinsky

Publications and source records attributed to D K Kalwinsky.

At least 55 records · Page 3Linked to original sources
PubMed1986

Unfavorable presenting clinical and laboratory features are associated with CALLA-negative non-T, non-B lymphoblastic leukemia in children.

Twenty-four (5.7%) of 424 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have blast cells that expressed HLA-DR antigens but not the common ALL antigen (CALLA), E-rosette receptors, T-cell antigens, or cytoplasmic or surface immunoglobulins. Each of the eight cases tested expressed the B-cell associated antigen B4, but not B1 or B2 antigen. Myeloid-associated antigens were not present in any of the 10 cases tested. By comparison with common (CALLA+ B-cell precursor) ALL, patients having this immunophenotype were more likely to be children less than 2 yr of age (p less than 0.001), to have higher initial leukocyte counts (p less than 0.001), and to have blast cells with a DNA index less than 1.16 (p = 0.05), a pseudodiploid karyotype (p = 0.01) and a chromosomal translocation (p = 0.003). The presence of any chromosomal translocation in these CALLA- ALL was related to measures of increased leukemic cell burden including higher leukocyte counts, larger liver and spleen sizes and higher serum lactic dehydrogenase levels. While the patients were entered into several treatment arms of two protocols, the CALLA- cases appeared to have lower remission rate (p = 0.06) and shorter event-free survival time (p = 0.05) than did those with common ALL. The association with clinical and laboratory features of known adverse prognostic significance provides some explanation for the poor treatment outcome of CALLA- ALL.

Antigens, Neoplasm↗
PubMed1986

Cytogenetic features and serum lactic dehydrogenase level predict a poor treatment outcome for children with pre-B-cell leukemia.

Leukemic cells from 89 (24%) of 369 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have a pre-B immunophenotype. By comparison with blasts having the common ALL phenotype, the pre-B cells were more likely to have a DNA index less than 1.16 (P = 0.02), a pseudodiploid karyotype (P less than 0.001), and a chromosomal translocation (P = 0.001). Increased serum lactic dehydrogenase levels (P = 0.001) were also characteristic of pre-B ALL; otherwise, the clinical and laboratory features of the two groups were similar. A nonrandom chromosomal translocation, t(1;19)(q23;p13.3), was identified in blast cells from 16 (23%) of the 70 patients with pre-B ALL and adequate chromosome banding studies; different translocations were found in 11 of the remaining patients. The presence of any chromosomal translocation in the pre-B group was significantly related to a higher leukocyte count, an increased level of serum lactic dehydrogenase, an increased percentage of S-phase cells, black race, and a blast cell DNA index less than 1.16. Four presenting features were found to confer an increased risk of treatment failure among pre-B patients: pseudodiploidy, chromosomal translocation, black race, and higher serum lactic dehydrogenase level. In a multivariate analysis, pseudodiploidy emerged as the strongest factor for predicting relapse in pre-B ALL. The frequent association of chromosomal abnormalities of known adverse prognostic significance and high serum lactic dehydrogenase levels with pre-B-cell ALL explains, at least in part, the poor treatment outcome reported for children with this subtype of leukemia.

Adolescent↗
PubMed1986

Phase I-II study of continuous-infusion high-dose human lymphoblastoid interferon and the in vitro sensitivity of leukemic progenitors in nonlymphocytic leukemia.

Twelve pediatric patients with nonlymphocytic leukemia were treated for 10 days with high-dose (15, 20, or 30 million U/m2/day) human lymphoblastoid interferon (Wellferon) administered by continuous iv infusion. Nine children had acute nonlymphocytic leukemia (ANLL) in relapse, two had Philadelphia chromosome-positive chronic myelocytic leukemia in myeloblastic crisis, and one had juvenile chronic myelocytic leukemia. Blast cell counts in the peripheral blood decreased in five patients with ANLL treated with the higher interferon doses; however, there was no evidence of an antileukemic effect in the marrow. Dose-limiting toxicity, which included malaise, hepatotoxicity, and coagulation abnormalities, was observed in patients given 20 or 30 million U/m2/day. Studies of the growth of leukemic progenitor cells in vitro in the presence of interferon disclosed a concentration-related inhibition of colony formation. Patients who had a decrease in peripheral blast cell counts demonstrated greater in vitro inhibition of clonogenic leukemic progenitors than patients whose blast cell counts did not decrease. However, the serum interferon concentrations in patients given clinically tolerable doses were lower than those concentrations which inhibited leukemic cell growth in vitro by a median of 42% (1000 U/ml). This study failed to demonstrate clinically significant antileukemic activity against nonlymphocytic leukemia in patients given high-dose constant-infusion interferon, and the toxicity of this approach was prohibitive.

Adolescent↗
PubMed1986

Chromosomal translocations play a unique role in influencing prognosis in childhood acute lymphoblastic leukemia.

Certain types of chromosomal abnormalities have been shown to exert strong independent influence on treatment outcome in acute lymphoblastic leukemia (ALL). To identify the changes most closely associated with prognosis, we analyzed the completely banded blast cell karyotypes of 161 children with this disease. One hundred twenty-five cases had one or more chromosomal abnormalities, with 45 showing translocations. The frequency of translocations was highest (58%) among patients with pseudodiploid karyotypes and lowest (0%) in the hyperdiploid group defined by 51 or more chromosomes. During the maximum 6-year follow-up period, 30 of the 45 patients with a translocation failed therapy, compared with only 27 of the 116 who lacked this feature. Life-table estimates of event-free survival indicate that only 14% of the translocation group will be in complete remission at 3 years. The percentages of failures associated with random and nonrandom translocations were virtually identical (68% v 65%). When entered in a Cox proportional hazards model with seven other types of chromosomal abnormalities, and then with 11 clinical and laboratory variables of known prognostic value in ALL, translocation emerged as the strongest single predictor of treatment outcome (P less than 0.0001). The model indicated that translocation increases the risk of treatment failure six times by comparison with the absence of this feature. These findings offer an explanation for the majority of early treatment failures in childhood ALL, including those previously attributed to ploidy classification.

Child↗
PubMed1986

Correlation of drug sensitivity in vitro with clinical responses in childhood acute myeloid leukemia.

Clonogenic cells from 41 children with newly diagnosed acute myeloid leukemia (AML) were tested in vitro for their sensitivity to cytarabine (Ara-C) and daunorubicin (DNR). The findings were then compared with the patients' responses to induction chemotherapy that uniformly included Ara-C and DNR. Light-density marrow cells were incubated with either or both drugs for one hour and cultured over leukocyte feeder layers; clusters and colonies were scored on days 7, 10, and 14. Only the percentage of cell kill in the presence of 1.8 mumol/L DNR was significantly associated with responses to induction therapy: median of 45% (range, 0% to 98%) for patients achieving complete remission v 16% (range, 4% to 23%) for nonresponders (P = .007). The relationship between clonogenic cell kill less than or equal to 23% and clinical responses was striking. Of the 11 evaluable patients with in vitro findings in this category, ten either failed induction therapy or relapsed within 1 year after attaining remission. Kaplan-Meier analysis of relapse-free survival times indicated longer durations of remission for patients whose blast cells showed increased sensitivity in vitro to Ara-C alone, DNR alone, or a combination of the two agents. Seven of 11 patients with cell kills of greater than or equal to 49% in the presence of 1.25 mumol/L Ara-C remain free of leukemia, compared with only one of 12 whose cells were less sensitive to the drug (P = .006). We conclude that the in vitro sensitivity of clonogenic leukemic progenitors to DNR and Ara-C correlates with treatment outcome in children with newly diagnosed AML.

Adolescent↗
PubMed1985

Mycotic cervical lymphadenitis following oral mucositis in children with leukemia.

Four children developed mycotic cervical lymphadenitis while receiving cytotoxic chemotherapy for acute leukemia. Neutropenia, oral mucositis, and broad-spectrum antibiotic administration preceded the appearance of lymphadenitis in each case. Enlarged tender cervical lymph nodes of mycotic origin were not clinically distinguishable from lymphadenitis of bacterial or viral origin. Although cervical lymphadenitis was the initial clinical manifestation of deep fungal infection, computerized tomography of the chest and abdomen subsequently demonstrated asymptomatic pulmonic, splenic, or hepatic lesions characteristic of fungal abscesses in all four children. These findings demonstrate the importance of microbiologic identification of the etiologic agents of cervical lymphadenitis following mucositis and neutropenia in children with leukemia.

Acute Disease↗
PubMed1985

Periodic acid-Schiff stain in childhood acute lymphoblastic leukemia: lack of independent prognostic value.

The authors reviewed 250 consecutive children with ALL to determine if the periodic acid-Schiff (PAS) score was a useful, independent predictor of time to failure. PAS stains were scored from 0 to 400 and divided into low- and high-score groups using a variance-ratio test (F test) to optimize any effect of PAS on prognosis. Although the effect of PAS score considered alone approached significance for time to failure, the PAS score lost all significance when the patients were divided into standard-risk and high-risk groups on the basis of peripheral white count, central nervous system involvement, mediastinal mass, or E-rosette positivity at diagnosis. A Cox regression analysis was performed on a subgroup of 198 patients for whom cytogenetic studies were also available. The PAS score again approached the level of significance when considered alone but was of no significance after the effects of peripheral white count, pseudodiploidy, mediastinal mass, and E-rosette positivity were removed. The authors conclude that the PAS stain has no independent prognostic significance in childhood ALL.

Adolescent↗
PubMed1985

Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia.

In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combinations of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distention, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.

Adolescent↗
PubMed1985

Clinical relevance of lymphoblast biological features in children with acute lymphoblastic leukemia.

Improvements in therapy for childhood acute lymphoblastic leukemia (ALL) have led us to reevaluate the prognostic significance of lymphoblast characteristics at diagnosis. From application of univariate and multivariate statistical methods, we determined the relationship of five blast cell features to treatment outcome in 250 patients who were enrolled in two clinical trials at this center from May 1979 through April 1982. Karyotype ploidy, lymphoblast morphology, and immunophenotype were each significantly related to prognosis as measured by time to failure, while periodic acid-Schiff reactivity and glucocorticoid receptor number lacked prognostic implication for this patient population. In addition, clinical features of initial WBC count, age, and race were also significant independent variables in predicting treatment response. By multivariate analysis, both ploidy and morphology contributed prognostic information to a clinical model based on WBC count, age, and race. If the model was adjusted for impact of ploidy, however, French-American-British morphology no longer contributed additional prognostic information. Our findings suggest that many traditional biological features used to estimate prognosis in ALL can be discarded in favor of clinical features (leukocyte count, age, and race) and cytogenetics (ploidy) for planning of future clinical trials.

Adolescent↗
PubMed1985

Central nervous system leukemia in children with acute nonlymphoblastic leukemia.

Factors contributing to the development of central nervous system (CNS) leukemia, and the impact of leukemic involvement of this site on subsequent remission length, were determined in 184 children with acute nonlymphoblastic leukemia who had been treated in two successive clinical trials. Preventive CNS therapy in both studies consisted of intrathecal methotrexate (12 mg/m2) given monthly during the first six months of therapy and then every three months until all treatment was stopped. Children with CNS leukemia at diagnosis or relapse were given intrathecal chemotherapy weekly for four weeks and then monthly throughout the remainder of the treatment course. Those continuing in complete remission received 2,400 rad cranial irradiation plus five doses of intrathecal methotrexate before cessation of therapy. The 38 children (20.7%) with CNS leukemia at diagnosis were more likely to have an initial leukocyte count greater than or equal to 25 X 10(9)/L (P = .01) and age less than 2 years (P = .03). The presence of CNS leukemia at diagnosis did not adversely affect the remission induction rate (P = .13) or the length of complete remissions (P = .73). CNS relapse ended initial remissions in 11 patients only and did not preclude subsequent long-term survival, as four of these children are off therapy and in second complete remission for 33+ to 78+ months. Three features at diagnosis were predictive of CNS relapse: monocytic or myelomonocytic leukemia (P = .002); age less than 2 years (P = .0001); and leukocyte count greater than or equal to 25 X 10(9)/L (P = .012). By stepwise Cox regression analysis, each factor was found to have independent predictive value. Despite the apparent effectiveness of intrathecal methotrexate as preventive CNS treatment, our findings indicate that more effective prophylaxis is needed for patients with features predisposing to CNS relapse.

Acute Disease↗
PubMed1985

A novel treatment of childhood lymphoblastic non-Hodgkin's lymphoma: early and intermittent use of teniposide plus cytarabine.

We treated 24 children and adolescents with stage III or IV lymphoblastic non-Hodgkin's lymphoma, using a protocol designed for patients with poor-prognosis acute lymphoblastic leukemia (ALL). Early therapy consisted of teniposide plus cytarabine administered before and immediately after prednisone, vincristine, and asparaginase. The two-drug combination was also given intermittently with continuous 6-mercaptopurine and methotrexate during the first year of continuation chemotherapy. Periodic intrathecal methotrexate and delayed cranial irradiation were used to prevent central nervous system involvement. Anthracycline compounds, alkylating agents, high-dose methotrexate, and involved-field irradiation were not used in any phase of treatment. Twenty-two (96%) of the 23 evaluable patients achieved complete remission. With a median follow-up of 2 1/2 years, only four patients have relapsed; the remainder have been disease-free for eight months to more than five years. The projected four-year continuous complete remission rate is 73% for all patients and 79% for the 19 with mediastinal involvement at diagnosis. These results demonstrate that use of teniposide plus cytarabine with an otherwise conventional plan of ALL therapy is an effective approach to the treatment of childhood lymphoblastic lymphoma.

Adolescent↗
PubMed1984

Impact of treatment efficacy on the prognostic value of glucocorticoid receptor levels in childhood acute lymphoblastic leukemia.

Glucocorticoid receptor (GR) levels were quantitated in leukemic blasts from bone marrow aspirates of 249 children with acute lymphoblastic leukemia (ALL) who were entered on two St. Jude Total Therapy Studies. Of these, 235 were evaluable for analysis of the relation of GR levels to clinical outcome. For the 42 patients in the earlier Total Therapy Study IX, lower GR levels (less than 16,000 sites/cell) were associated with both induction failure and more frequent relapse (p less than 0.01) [Cancer Research, Vol. 42, p. 4801 (1982)]. When patients with 'high-risk' features (leukocyte count greater than 100 X 10(3)/mm3, positive erythrocyte rosette test, central nervous system involvement, and mediastinal mass) were excluded, lower receptor levels were still associated with early and more frequent relapse (p less than 0.02). The other 193 evaluable patients were consecutively admitted to Total Therapy Study X, in which patients with 'standard-risk' or 'high-risk' features were assigned to separate protocols--XS and XH, respectively. Induction chemotherapy in both protocols consisted of prednisone, vincristine and L-asparaginase; patients in the XH protocol received additional epipodophyllotoxin (VM-26) and cytosine arabinoside twice a week for 2 weeks preceding the conventional induction therapy. To compare the prognostic value of GR level in Study X with that of Study IX (which included both 'high-risk' and 'standard-risk' patients but did not separate them into different protocol groups), children in the XH and XS protocols were analysed together. The proportion of patients with 'standard-risk' features was the same in the two studies: 69% in Study IX and 73% in Study X. In Study X, which had a significantly better treatment result (p less than 0.001), lower receptor levels were not associated with induction failure, but were correlated with more frequent relapse (p less than 0.05). When patients in XH and XS protocols were analysed separately, however, receptor levels were no longer related to treatment outcome. Thus, GR level in childhood ALL has prognostic value, but it is not an independent factor and its importance is related to the efficacy of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Auer rods in mature granulocytes: a unique morphologic feature of acute myelogenous leukemia with maturation.

The authors observed Auer rods in mature neutrophils, bands, and metamyelocytes in two children with AML with maturation (FAB M2). In order to determine if this rare finding was characteristic of AML M2, the authors reviewed the bone marrows and peripheral blood smears of 50 children with AML M2 and 50 children with other AML subtypes (FAB M1, M3, M4, and M5). They found Auer rods in mature neutrophils and band forms in 10 of 50 patients (20%) with AML M2 but in none of 50 patients with non-M2 AML. This finding was not related to the frequency of mature cells in the specimen or to the frequency of Auer rods in blasts. Cytogenetics did not show a consistent abnormality. The presence of Auer rods in mature granulocytes is unique to FAB M2 AML in the authors' series and supports the concept that in AML at least some of the mature myeloid cells are involved in the leukemic process.

Adolescent↗
PubMed1984

Pseudallescheria boydii in a patient with acute lymphoblastic leukemia.

Pseudallescheria boydii, a common soil organism, is best known as the causative agent of mycetoma. Isolation of the organism from sites other than the extremities is relatively uncommon. However, the use of corticosteroids and cancer chemotherapy has been associated with an increasing frequency of localized superinfection as well as disseminated disease. Recently, an increased number of disseminated P boydii infections, primarily associated with immunosuppressed patients, has been reported in the literature. We diagnosed an additional case of P boydii in a 16-year-old boy who had acute lymphoblastic leukemia and manifested a disseminated infection during reinduction chemotherapy. The unusual features of this case were the extent of organ involvement, which was more wide-spread than previously noted in the literature, and the presence of conidia in sections of an endocardial thrombus.

Adolescent↗
PubMed1984

Failure of late intensification therapy to improve a poor result in childhood lymphoblastic leukemia.

This clinical study, begun in 1975, tested the efficacy of early and delayed intensification treatments in children with acute lymphoblastic leukemia. Regardless of presenting features, all patients received 4 weeks of conventional induction therapy with daily prednisone and weekly vincristine and daunorubicin. One-third were randomized to receive, in addition, two doses of asparaginase during induction therapy, while another one-third received four doses of both asparaginase and cytarabine after remission induction. Preventive central nervous system therapy uniformly included 2400 rads cranial irradiation and five doses of intrathecal methotrexate. Remissions were maintained with daily p.o. mercaptopurine and weekly i.v. methotrexate. Of the 277 assessable patients, 254 (92%) entered complete remission, and 102 (37%) remain clinically free of leukemia for 4.6 to 8.0 years (median, 6.3 years). The three treatment groups showed no significant differences in either remission induction rate or outcome, even when the analysis was based on risk assignment. A "late intensification" phase of therapy, added to the maintenance protocol for 65 patients who had been in continuous complete remission for 14 to 30 months, failed to extend remission durations, as judged from statistical comparison with matched controls (p = 0.84). When tested as a time-dependent covariate in the Cox proportional-hazards model, delayed intensification again showed no important effect on duration of complete remission. We conclude that limited early or aggressive late intensification of therapy, as described here, does not improve outcome in childhood acute lymphoblastic leukemia.

Adolescent↗
PubMed1983

Glucocorticoid receptors in childhood acute non-lymphocytic leukemia.

Using a whole-cell assay, we found glucocorticoid receptors (GR) in all 43 consecutive assessable children with newly diagnosed acute non-lymphocytic leukemia (ANLL). The receptor levels ranged from 2146 to 81,308 sites/cell (median = 18,105); these results were similar to those for acute lymphocytic leukemia. Receptor levels were not related to any of these clinical or biological features at diagnosis: age, sex, race, initial leukocyte count, liver or spleen size, presence of CNS disease or Auer rods, [3H] thymidine ( [3H]TdR) labelling index, French-American-British morphology or terminal deoxynucleotidyl transferase activity. Receptor levels also were not related to the initial treatment response or remission duration after therapy that did not include a glucocorticoid. We conclude that GR level has no clinical utility as a marker protein in childhood ANLL.

Acute Disease↗