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J T Sandlund

Publications and source records attributed to J T Sandlund.

At least 55 records · Page 3Linked to original sources
PubMed1998

Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia.

The purpose of this study was to determine the incidence of and pharmacokinetic parameters associated with the development of transient encephalopathy following the administration of high-dose methotrexate and intrathecal chemotherapy in children with acute lymphoblastic leukemia (ALL). Two hundred and fifty-nine children with newly diagnosed ALL treated on one of two consecutive trials were analyzed. Presenting features in patients who developed transient encephalopathy were compared with those of patients who did not experience this event. For each patient who developed transient encephalopathy, methotrexate pharmacokinetic parameters were compared with those of matched controls. The cumulative incidence of acute encephalopathy was 3% (SE 1%) at 1 year and was associated with age greater than or equal to 10 years at diagnosis. Pharmacokinetic data did not differ between patients who developed transient encephalopathy and those who did not. The majority of patients had no long-term sequelae and were able to receive further courses of methotrexate without modification. Transient focal neurologic deficits occur in about 3% of children with ALL following the administration of intravenous and intrathecal methotrexate. These events cannot be predicted by pharmacokinetic parameters Of methotrexate disposition. However, these events are generally benign, suggesting that patients who experience acute encephalopathy should continue to receive this important chemotherapeutic agent.

Adolescent↗
PubMed1998

Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia.

Asparaginase is an effective antileukemic agent and is included in most front-line protocols for pediatric acute lymphoblastic leukemia (ALL) worldwide; however, allergic reactions to asparaginase may be dose-limiting. We evaluated plasma anti-asparaginase antibody concentrations in a cohort of children with newly diagnosed ALL, who did and who did not exhibit clinical hypersensitivity, after Escherichia coli (E. coli) asparaginase therapy. Thirty-five children who received asparaginase 10000 IU/m2 i.m. three times weekly for nine doses as part of both multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Twenty-two patients experienced initial allergic reactions to asparaginase during continuation (n=20) or reinduction (n=2) phases and 13 children did not exhibit any reaction. An enzyme-linked immunosorbent assay (ELISA) was used to measure anti-asparaginase antibodies in plasma samples, diluted 1:3200, using E. coli asparaginase as the antigen. The median anti-asparaginase antibody concentration (OD at 1:3200 dilution) increased from 0.039 at induction to 0.506 at reinduction in patients who exhibited clinical hypersensitivity (P = 0.0002). By comparison, median antibody level increased from 0.011 to 0.032 OD at identical time points in patients who did not react to asparaginase (P = 0.02). Both post-induction and post-reinduction anti-asparaginase antibody levels were higher in reacting than in nonreacting patients (P = 0.004 and P = 0.01, respectively). Antibody levels were inversely related to the time elapsed between the reaction and sampling (P = 0.011). Although anti-asparaginase antibody levels increased from the post-induction plasma sample to the post-reinduction sample in 28 of 35 patients regardless of whether they exhibited clinical hypersensitivity, patients with hypersensitivity reactions had higher antibody levels than did identically treated control patients at comparable time points in therapy. Therefore, antibody analysis may be of clinical value in predicting future hypersensitivity.

Adolescent↗
PubMed1998

Primary central nervous system lymphoma in a child with acute B-cell lymphoblastic leukaemia: consecutive Epstein-Barr virus-related malignancies.

Primary central nervous system lymphoma (PCNSL), observed among immunocompromised AIDS patients, has not been reported during chemotherapy for acute lymphoblastic leukaemia (ALL). We report a case of PCNSL occurring in a child receiving intensive multiagent chemotherapy for B-cell ALL. In situ hybridization studies demonstrated Epstein-Barr virus genome in both tumours, suggesting a possible link between the two diseases. The clinical response of the PCNSL to conservative therapy highlights the importance of accurately diagnosing such EBV-related disorders, especially in patients where immune compromise can be reversed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia.

PURPOSE: To reassess the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: We prospectively studied 334 newly diagnosed cases of this disease, using a comprehensive panel of antibodies that represented five myeloid cluster groups (CD13, CD14, CD15, CD33, and CD65). Blast cells were tested for ETV6 and MLL rearrangement using Southern blot analysis. RESULTS: CD13 was expressed in 13.7% of cases, CD14 in 1%, CD15 in 6.6%, CD33 in 16%, and CD65 in 9.7%. Approximately one third of cases (31.4%) expressed one or more of these antigens (B-cell precursor, 31.9%; T-cell, 28.8%), while 10.5% expressed two or more (B-cell precursor, 11.3%; T-cell, 6.1%). Among the B-cell precursor leukemias, myeloid-associated antigen expression was significantly associated with a lack of hyperdiploidy and rearrangements of ETV6 or MLL gene. Most of the cases with MLL rearrangements (82%) expressed CD65, CD15, and CD33, either alone or in combination, whereas 48% of those with a rearranged ETV6 gene expressed CD13, CD33, or both. Myeloid-associated antigen expression did not correlate with event-free survival, whether the analysis was based on any of the five antigens in our panel or on the three more commonly tested antigens (CD13, CD33, and CD65). Importantly, this finding was not affected by exclusion of patients with ETV6 or MLL gene rearrangements. CONCLUSION: Even though blast cell expression of myeloid-associated antigen expression shows significant associations with specific genetic abnormalities, it lacks prognostic value in childhood ALL.

Adolescent↗
PubMed1997

Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia.

BACKGROUND: Recombinant human granulocyte colony-stimulating factor PO1 CA-20180ilgrastim) hastens the recovery from neutropenia after P30 CA-21765emotherapy, but its role in the management of childhood leukemia is unclear. METHODS: We randomly assigned 164 patients with acute lymphoblastic leukemia (age range, 2 months to 17 years) to receive placebo or G-CSF (10 microg per kilogram of body weight per day subcutaneously), beginning one day after the completion of remission-induction therapy and continuing until the neutrophil count was greater than or equal to 1000 per cubic millimeter for two days. The clinical and laboratory effects of this therapy were documented for 21 days. The area under the plasma G-CSF concentration-time curve was measured on days 1 and 7 in both groups. RESULTS: Responses to the growth factor could be assessed in 148 patients (73 in the G-CSF group and 75 in the placebo group). G-CSF treatment did not significantly lower the rate of hospitalization for febrile neutropenia (58 percent in the G-CSF group vs. 68 percent in the placebo group; relative risk, 0.85; 95 percent confidence interval, 0.59 to 1.16), increase the likelihood of event-free survival at three years (83 percent in both groups), or decrease the number of severe infections (five in the G-CSF group vs. six in the placebo group). Patients treated with G-CSF had shorter median hospital stays (6 days vs. 10 days, P=0.011) and fewer documented infections (12 vs. 27, P=0.009). The median total costs of supportive care were similar in the G-CSF and placebo groups ($8,768 and $8,616, respectively). Among patients who did not have febrile neutropenia during the first week of G-CSF or placebo injections, higher systemic exposure to the growth factor on day 7 was significantly related to a lower probability of subsequent hospitalization (P=0.049). CONCLUSIONS: G-CSF treatment had some clinical benefit in children who received induction chemotherapy for acute lymphoblastic leukemia, but it did not reduce the rate of hospitalization for febrile neutropenia, prolong survival, or reduce the cost of supportive care.

Adolescent↗
PubMed1997

Higher frequency of glutathione S-transferase deletions in black children with acute lymphoblastic leukemia.

The genetic polymorphisms in human glutathione S-transferases (GST) M1 and T1 have been associated with race, disease risk, and outcome of some adult cancers. Also, there are racial differences in the incidence and characteristics of childhood acute lymphoblastic leukemia (ALL). Our objectives were to compare the frequency of the null genotype for GSTM1, GSTT1, or both in children with ALL to that in healthy controls, and to determine whether GST genotype was associated with treatment outcome and prognostic factors. We studied GSTM1 and GSTT1 genotypes in somatic cell DNA from black children and white children with ALL and in 416 healthy controls, using a polymerase chain reaction technique. Ninety of 163 (55.2%) white ALL patients and 14 of 34 (41.2%) black patients were GSTM1 null, frequencies not significantly different (P = .19) than healthy controls (53.5% in whites and 27.6% in blacks), although there was a trend toward more null genotypes in black ALL patients. Twenty-three of 163 (14.1%) white ALL patients and 12 of 34 (35.3%) black ALL patients were GSTT1 null, not different (P = .34) than the frequencies in healthy controls (15.0% in whites and 24.1% in blacks). However, the frequency of the "double-null" genotype, lacking both GSTM1 and GSTT1, was higher in black patients with ALL (8 of 34 or 23.5%) than in black controls (3.9%) (P = .0005), but this was not the case in white patients with ALL (10 of 163 or 6.1%) compared to white controls (8.0%) (P = .68). In stratified analyses, the GST double-null genotype was not associated with other characteristics that might differ between whites and blacks with ALL, such as age, T-lineage immunophenotype, presenting white blood cell count, DNA index, or insurance status. The null genotype for GSTM1, GSTT1, or both was not found to be a prognostic factor for disease-free survival or probability of hematologic remission; central nervous system relapse tended to be less common in those with the GSTM1 null genotype (P = .054). The double-null genotype for GSTM1 and GSTT1 is more common among blacks but not whites with childhood ALL. These data suggest that GST genotype, coupled with unidentified additional risk factors, may play a role in risk of childhood ALL in American blacks.

Adult↗
PubMed1997

XYY syndrome in children with acute lymphoblastic leukemia.

Certain constitutional chromosomal abnormalities increase the risk of malignancy and/or decrease treatment tolerance. We identified two patients with the XYY syndrome among a total of 444 male children with acute lymphoblastic leukemia who had complete cytogenetics studies. In both cases, the leukemic cell karyotype suggested a constitutional XYY abnormality that was confirmed in studies of lymphocytes obtained during remission. The incidence rate in our series is higher than that of the XYY syndrome in the general population (0.0045 vs. 0.001), but not significantly so. This finding and a literature review failed to confirm an increased frequency of the XYY syndrome among children with acute lymphoblastic leukemia. Both of our patients remain in remission 24 and 28 months, respectively, postdiagnosis. Their tolerance of intensive treatment, including high-dose methotrexate, suggests that the untoward treatment toxicity seen in patients with chromosomal abnormalities such as trisomy 21 does not extend to the XYY syndrome.

Adolescent↗
PubMed1997

Systemic hemophagocytosis masking the diagnosis of large cell non-Hodgkin lymphoma.

An 11-year-old female presented with clinical features suggestive of malignant histiocytosis: fever, weight loss, subcutaneous nodules, pulmonary infiltrates, adenopathy, and hepato-splenomegaly. On biopsy, lymph node and bone marrow demonstrated necrosis and extensive hemophagocytosis with no definitive evidence of malignancy: the subcutaneous nodules, however, demonstrated large-cell non-Hodgkin lymphoma. This clinicopathologic picture has been reported in adults, but not in children. Although serum G-CSF, M-CSF, and TNF levels were not elevated in this child, it is possible that other cytokines induced either directly or indirectly by the subcutaneous lymphoma resulted in hemophagocytosis.

Bone Marrow↗
PubMed1997

Small noncleaved cell lymphoma in an adolescent with the XYY syndrome.

A 19-year-old male was diagnosed with stage III abdominal small noncleaved cell (SNCC) non-Hodgkin lymphoma (NHL). Cytogenetic evaluation of the tumor revealed a complex karyotype which included the t(8;14)(q24;q32), classically associated with this lymphoma histotype, and an extra Y chromosome. After remission was obtained, cytogenetic analysis of bone marrow cells and PHA-stimulated peripheral blood lymphocytes disclosed a normal karyotype except for the persistence of an extra Y chromosome, diagnostic of the XYY syndrome. This is the first reported case of SNCC NHL in an adolescent with the XYY syndrome.

Aneuploidy↗
PubMed1997

Predominance and characteristics of Burkitt lymphoma among children with non-Hodgkin lymphoma in northeastern Brazil.

The purpose of this paper was to define the histologic distribution, clinical features, and treatment response of childhood non-Hodgkin lymphoma (NHL) in northeastern Brazil. We reviewed medical records and histopathologic studies of 98 children treated for NHL from 1980 to 1987 at a major pediatric cancer center in Recife, Brazil. Treatment outcome was evaluated in relation to tumor burden (stage and serum LDH) and type of therapy (LSA2L2 vs other multiagent chemotherapy). There was a striking predominance of the small noncleaved cell (Burkitt) subtype, which occurred in 92 of the 98 children and adolescents diagnosed with NHL. Subsequent analyses focused on these patients. The majority (n = 84) had advanced (stage III/IV) disease at diagnosis. The abdomen was the most common site of disease (84 cases); jaw involvement was rare (three cases). Five-year event-free survival (excluding treatment refusals) was significantly better for patients with limited vs advanced stage disease (75 +/- 14% vs 42 +/- 6%; P < 0.04). Elevated serum LDH (>500 U/l) was associated with a poorer outcome (P = 0.008). The type of chemotherapy did not affect EFS (P = 0.95). Only 39% of patients are long-term survivors, reflecting the high rate of septic deaths (25% of patients) and parental refusal/abandonment of therapy (10%). Epstein-Barr virus (EBV) was detected in tumor cells from eight of the 11 cases studied. In clinical presentation, these cases resemble sporadic Burkitt lymphoma, yet in their apparent responsiveness to LSA2L2 therapy and association with EBV, they do not. Childhood NHL in northeastern Brazil is predominantly of the Burkitt subtype, and is associated with clinical features that appear to distinguish it from the endemic and sporadic forms of this tumor. These cases may represent a third or intermediate subtype of Burkitt lymphoma.

Adolescent↗
PubMed1997

Philadelphia chromosome-positive acute lymphoblastic leukemia in children: durable responses to chemotherapy associated with low initial white blood cell counts.

To substantiate the reported sensitivity of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) to St Jude-type multiagent chemotherapy and to identify means of selecting patients most likely to benefit from such treatment, we analyzed the clinical and biologic characteristics of 12 patients with classic Ph+ ALL who were treated in either of two total therapy programs at St Jude Children's Research Hospital (1989-1994). Event-free survival estimates for this cohort were compared with historical data on 11 patients from an earlier total therapy study (Lancet 1994; 343: 331-332). The prognostic importance of age, white blood cell count and other presenting features was assessed by the logrank test in all 23 patients. Complete remissions were induced in 92% of the patients treated since 1989, compared with 82% of the historical control group (P > 0.05). There was essentially no difference in event-free survival between the study group and historical controls (4-year Kaplan-Meier estimates, 33 +/- 19% s.e. vs 36 +/- 13%). Further analysis of potentially informative risk factors identified a good-prognosis subgroup defined by an initial white blood cell count of < or =25 x 10(9)/l and a 4-year event-free survival of 73 +/- 19%. In conclusion, intensive multiagent chemotherapy offers an attractive therapeutic option for children and adolescents with Ph+ ALL and low presenting leukocyte count.

Adolescent↗
PubMed1997

Genetic studies of childhood acute lymphoblastic leukemia with emphasis on p16, MLL, and ETV6 gene abnormalities: results of St Jude Total Therapy Study XII.

To determine the frequency and prognostic significance of recently described genetic lesions in pediatric acute lymphoblastic leukemia (ALL), all cases with available leukemic cell samples treated on St Jude Study XII were analyzed by molecular techniques for alterations of the p16, MLL and ETV6 genes. Homozygous p16 deletion was seen in 36 of 155 cases, including 14 of 23 T cell cases, but had no prognostic value. Rearrangement of MLL was seen in nine of 170 cases (5%) and conferred a poor prognosis, with a 5-year EFS estimate of only 11 +/- 7%, compared with 74 +/- 5% for the germline MLL group (P=0.0001). By contrast, rearrangement of ETV6 was found in 35 cases (21%) and was significantly associated with a better outcome (5-year EFS estimates: 87 +/- 7% vs 64 +/- 6%). In a Cox regression model adjusted for age, DNA index, race, leukocyte count, treatment group, and CNS status, ETV6 rearrangement retained independent prognostic significance (two-sided P value 0.012). Thus, in this uniformly treated group of patients, we confirmed the unfavorable prognostic significance of MLL rearrangement and demonstrated the favorable impact of ETV6 rearrangement, suggesting that these factors be added to ALL risk classification schemes.

Carrier Proteins↗
PubMed1997

Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies.

Standard prophylaxis and treatment of malignancy-associated hyperuricemia in the USA has been allopurinol with vigorous hydration, urinary alkalinization and osmotic diuresis. Urate oxidase, the enzyme that converts uric acid to allantoin (a readily excreted metabolite that has 5- to 10-fold higher solubility than uric acid), is an alternative therapy; however, few published findings support this practice. Between February 1994 and December 1996, we administered non-recombinant urate oxidase (Uricozyme) to 126 children with newly diagnosed non-B cell acute lymphoblastic leukemia (ALL) during the first 5 days of chemotherapy with methotrexate, 6-mercaptopurine or both. Their blood levels of uric acid and other indicators of tumor lysis were measured at diagnosis and during treatment and then compared with findings in 129 similarly treated historical controls who had received allopurinol to control hyperuricemia. Clinical responses to urate oxidase were also determined in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid and significantly greater decreases in their blood uric acid levels than did the historical controls (median maximal level during treatment, 2.3 vs 3.9 mg/dl, P < 0.001). They also had lower creatinine (0.6 vs 0.7 mg/dl, P = 0.01) and blood urea nitrogen (11 vs 24 mg/dl, P < 0.001) levels. Similar findings were made in the eight cases of B cell ALL or non-Hodgkin lymphoma. None of the patients required dialysis for acute renal failure. Six (4.5%) of the 134 children given urate oxidase had allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effective uricolytic agent than allopurinol but is associated with acute hypersensitivity reactions, even in patients without a history of allergy.

Allopurinol↗
PubMed1997

Decision making by parents and healthcare professionals when considering continued care for pediatric patients with cancer.

PURPOSE/OBJECTIVES: To better define the treatment-related decisions considered most difficult by parents of pediatric patients with cancer and the factors that influenced their final decisions. DESIGN: Retrospective-descriptive design. SETTING: Pediatric oncology institution in the mid-southern region on the United States. SAMPLE: 39 parents representing 37 of 83 eligible families, 16 attending physicians, three nurses, and two chaplains. METHODS: Parent participants responded by telephone to six open-ended interview questions and a 15-item questionnaire about factors that were important when making the decision to continue care. Healthcare professionals were interviewed face-to-face. MAIN RESEARCH VARIABLES: Most difficult treatment-related decisions; factors influencing decision making. FINDINGS: Parents reported 15 types of difficult decisions, the majority of which were made late in the course of treatment. Deciding between a phase I drug study or no further treatment (n = 14), maintaining or withdrawing life support (n = 11), and giving more chemotherapy or giving no further treatment (n = 8) were the most frequently reported difficult decisions. Parents rated "recommendations received from healthcare professionals" as the questionnaire factor most important in their decision making, and healthcare professionals rated "discussion with the family of the patient" as the most important factor. CONCLUSION: Parents of children or adolescents with cancer and their healthcare providers face difficult treatment-related decisions, many of which occur late in the course of treatment. Parents and healthcare professionals cite similar factors in their decision making but differ in their ratings of the factors' importance. For parents, the information and recommendations they receive from healthcare professionals figure most frequently and most importantly in their decision making. For healthcare professionals, the certainty that the patient will not get better and discussions with the patient's family figure most importantly in their decision making. Once parents conclude that their child can not get better, they are more likely to choose noncurative options such as choosing no further treatment or withdrawing life support. IMPLICATIONS FOR NURSING PRACTICE: Nurses can help determine what information parents need in their decision making. Particular attention must be given to ways to communicate the likelihood of the their child's survival.

Adolescent↗
PubMed1996

Overt testicular disease at diagnosis is associated with high risk features and a poor prognosis in patients with childhood acute lymphoblastic leukemia.

BACKGROUND: The impact of overt testicular disease on survival was assessed among patients treated at the study institution for childhood acute lymphoblastic leukemia (ALL) over a 15-year period. To the authors' knowledge, the frequency of overt testicular involvement at diagnosis of ALL and its impact on treatment outcome have not been reported previously. METHODS: The medical records of all 651 boys with ALL enrolled on St. Jude Total Therapy Studies X-XIIIA (May 1979 to December 1993) were reviewed to determine the frequency of overt testicular involvement at diagnosis. The log rank test and sequential Cox regression analyses, adjusted for known adverse features, were used to compare event free and overall survival for patients with and without testicular leukemia. A matched-pairs analysis was then conducted for both outcome measures. RESULTS: Thirteen of the 651 male patients (1.9%) presented with overt testicular leukemia. Compared with the other patients, these 13 boys had a significantly higher frequency of infant or adolescent age at diagnosis, hyperleukocytosis, splenomegaly, and mediastinal mass; a poorer 5-year event free survival (38% [95% confidence interval (CI), 15.4-61.4%] vs. 58% [95% CI, 53.6-61.7%], P = 0.06, log rank test); and a significantly poorer 5-year overall survival (37% [95% CI, 14-60.4%] vs. 75% [95% CI, 71.3-78.4%], P = 0.002). The difference in overall, but not event free, survival was supported by sequential Cox regression analyses and by the matched-pairs analysis (P = 0.04). CONCLUSIONS: Overt testicular involvement with leukemia at diagnosis was associated with an adverse survival in boys with ALL. Testicular irradiation may not be necessary in those patients who present with overt testicular involvement. This finding merits prospective evaluation in a larger sample of similarly treated patients.

Adolescent↗
PubMed1996

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

Methotrexate (MTX) is one of the most widely used drugs for the treatment of childhood acute lymphoblastic leukemia (ALL) and is commonly given in high doses. However, the rationale for high-dose MTX (HDMTX) has been challenged recently. To determine whether higher MTX polyglutamate (MTXPG) concentrations in ALL blasts translate into greater antileukemic effects, 150 children with newly diagnosed ALL were randomized to initial treatment with either HDMTX (1,000 mg/m2 intravenously over 24 h) or lower-dose MTX (30 mg/m2 by mouth every 6 h x 6). ALL blasts accumulated higher concentrations of MTXPG and long-chain MTXPG (MTXPGLC) after HDMTX (P < 0.00001). Of 101 patients evaluable for peripheral blast cytoreduction, MTXPG concentrations were higher in patients whose blast count decreased within 24 h (P = 0.005) and in those who had no detectable circulating blasts within 4 days (P = 0.004). The extent of inhibition of de novo purine synthesis in ALL blasts was significantly related to the blast concentration of MTXPGLC (IC95% = 483 pmol/10(9) blasts). The percentage of patients with 44-h MTXPGLC exceeding the IC95% was greater after HDMTX (81%) than LDMTX (46%, P < 0.0001). These data indicate that higher blast concentrations of MTXPG are associated with greater antileukemic effects, establishing a strong rationale for HD-MTX in the treatment of childhood ALL.

Adolescent↗