PubMed Health⌕ Search

Biomedical subjects

C H Pui

Publications and source records attributed to C H Pui.

At least 217 records · Page 12Linked to original sources
PubMed1992

Update of St Jude Study XI for childhood acute lymphoblastic leukemia.

We treated 358 children with non-B-cell acute lymphoblastic leukemia with intensive multiagent chemotherapy (St. Jude Study XI) in a risk-directed study which used very intensive induction and consolidation therapy followed by continuation treatment comprised of rotating drug pairs given for the entire duration of therapy (except for a third of lower-risk patients). CNS irradiation was reserved for a subset of patients at higher risk of treatment failure. All patients received triple intrathecal chemotherapy (hydrocortisone, ara-C, methotrexate) for prevention of CNS leukemia. At a median follow-up of almost 5 years (all patients are off therapy for 8 months or more), the estimated 5-year event-free survival rate is 72% +/- 4%. The isolated CNS relapse rate is 5% and there has been only a single testicular relapse. The high incidence of secondary acute myeloid leukemia which we previously associated with use of epipodophyllotoxins were highly associated with a single treatment regimen featuring 6 consecutive weeks of epipodophyllotoxin therapy. Study XI was significantly more effective than all previous St. Jude Total Therapy studies (especially for higher risk patients), could be delivered mostly in the outpatient setting, and, except for a single regimen, was largely free of serious side effects.

Acute Disease↗
PubMed1992

Childhood malignant non-Hodgkin lymphomas of uncommon histology.

Uncommon histologies were identified in 36 of 1336 cases (2.7%) of newly diagnosed childhood non-Hodgkin lymphoma (NHL). Seventeen cases were classified as follicular (six cases as mixed small and large cell, nine as large cell, and two as small non-cleaved cell) and 19 cases as diffuse (18 cases as mixed small and large cell, and one as small cell lymphocytic). The follicular pattern group included a preponderance of male patients; the median age at diagnosis was 11.7 years. These children presented primarily with low-stage disease involving lymph nodes or tonsils. All patients except one achieved complete remission and remain disease-free for 11 months to 18.8 years (actuarial 5-year event-free survival, 94%). The group with diffuse histologies was similar in sex ratio, age at diagnosis (median = 12.1 years), and nodal involvement, but tended to have more advanced-stage disease. Moreover, only 14 of 19 (74%) children with diffuse intermediate-grade histologies are alive in continuous complete remission (actuarial 5-year event-free survival, 70%). These results suggest that follicular pattern childhood NHL has an excellent prognosis, whereas cases with diffuse intermediate-grade histology are prognostically similar to those with diffuse high-grade histologies.

Adolescent↗
PubMed1992

Differences in teniposide disposition and pharmacodynamics in patients with newly diagnosed and relapsed acute lymphocytic leukemia.

Teniposide, a widely used investigational anticancer drug, is extensively bound to plasma proteins (greater than 95%). The present study evaluated the clearance and pharmacodynamics of total and unbound teniposide in patients with acute lymphocytic leukemia who were either in first complete remission or who had relapsed and achieved a subsequent complete remission. When compared to values of patients in first remission, the mean total systemic clearance of teniposide in relapsed patients was significantly lower at the time remission reinduction therapy was initiated, but increased to values greater than first remission patients after a subsequent remission was achieved. However, the mean clearance of unbound teniposide (ml/min/m2) was 3-fold lower in relapsed patients during reinduction therapy (1224 vs. 4261, P less than .0001), and improved but remained low after these patients achieved a subsequent remission (1965, P = .025). Changes in plasma protein binding accounted for the increase in total clearance when unbound clearance decreased. Continuous therapy with L-asparaginase was the major treatment difference in those patients with hypoalbuminemia and lower clearance of unbound teniposide. In 15 evaluable patients in complete remission, there was a statistically significant (P = .039) linear correlation between the percentage decrease in white blood cell count and the systemic exposure (AUC) to unbound teniposide, with higher exposure associated with a greater decrease in white blood cell count. There was not a significant correlation between the percent decrease in white blood cell count and the dosage given or the systemic exposure to total teniposide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia.

BACKGROUND AND METHODS: Treatment of cancer with the epipodophyllotoxins (etoposide and teniposide) has been linked to the development of acute myeloid leukemia (AML) in children and adults, but the factors that might influence the risk of this complication of therapy are poorly defined. We therefore assessed the importance of potential risk factors for secondary AML in 734 consecutive children with acute lymphoblastic leukemia who attained complete remission and received continuation (maintenance) treatment according to different schedules of epipodophyllotoxin administration. RESULTS: Secondary AML was diagnosed in 21 of the 734 patients, in 17 of whom this complication was the initial adverse event. Prolonged administration of epipodophyllotoxin (teniposide with or without etoposide) twice weekly or weekly was independently associated with the development of secondary AML (P less than 0.01 by Cox regression analysis). The overall cumulative risk of AML at six years was 3.8 percent (95 percent confidence interval, 2.3 percent to 6.1 percent); but within the subgroups treated twice weekly or weekly, the risks were 12.3 percent (95 percent confidence interval, 5.7 percent to 25.4 percent) and 12.4 percent (95 percent confidence interval, 6.1 percent to 24.4 percent), respectively. In the subgroups not treated with epipodophyllotoxins or treated with them only during remission induction or every two weeks during continuation treatment, the highest cumulative risk was 1.6 percent (95 percent confidence interval, 0.4 percent to 6.1 percent). After adjustment for treatment frequency, there was no apparent relation between the total dose of epipodophyllotoxins and the development of secondary AML. The relative hazard of etoposide as compared with teniposide could not be determined. CONCLUSIONS: The risk of epipodophyllotoxin-related AML depends largely on the schedule of drug administration. Other factors, including the cumulative dose of epipodophyllotoxin, radiotherapy, and the initial biologic features of the leukemic blast cells, do not appear to have critical roles.

Acute Disease↗
PubMed1991

Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse.

To define the clinical and biologic significance of childhood acute mixed-lineage leukemia diagnosed by stringent criteria, we studied 25 cases of acute lymphoblastic leukemia expressing greater than or equal to 2 myeloid-associated antigens (My+ ALL), and 16 cases of acute myeloid leukemia expressing greater than or equal to 2 lymphoid associated antigens (Ly+ AML). These cases represented 6.1% of 410 newly diagnosed ALLs (two treatment protocols) and 16.8% of 95 AMLs (two protocols). T-lineage--associated antigens were identified in 9 of the My+ ALL cases and in 14 of those classified as Ly+ AML; all but 1 of the 19 cases that could be subclassified had an early thymocyte stage of differentiation. The My+ ALL cases had an increased frequency of French-American-British (FAB) L2 morphology (36%); the Ly+ AML cases were characterized by FAB M1 or M2 morphology, low levels of myeloperoxidase reactivity and combined populations of myeloperoxidase-positive large blasts and small blasts generally of hand-mirror morphology. Karyotypic abnormalities included t(9;22)(q34;q11) in three cases of My+ ALL, 11q23 translocations in two cases of My+ ALL, and 14q32 translocations in three My+ ALL and five Ly+ AML cases. Mixed-lineage expression lacked prognostic significance in either ALL or AML; however, the findings indicate that some patients with Ly+ AML may respond to prednisone, vincristine, and L-asparaginase after failing on protocols for myeloid leukemia. At relapse, two My+ ALLs had converted to AML and two Ly+ AMLs to ALL; one case in each group showed complete replacement of the original karyotype. Acute mixed-lineage leukemia does not adequately describe the heterogeneity of the cases identified in this study and should be replaced by a set of more restrictive terms that indicate the unique biologic features of these leukemias.

Adolescent↗
PubMed1991

Clinical and biologic features of childhood T-cell leukemia with the t(11;14).

Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations.

Adolescent↗
PubMed1991

Cranial nerve palsy in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Forty-five children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma had cranial nerve palsy (CNP) as a complication of their disease. Twenty-two of these children had CNP initially and 23, at relapse, with or without previous hematologic relapse. Only one of the 23 patients with CNP at relapse was a long-term survivor. In contrast, 11 of the 22 children who had CNP initially survived in remission for 3+ months to 13+ years. Two factors are associated with an improved outcome for patients with CNP at diagnosis: treatment after 1979 (P less than 0.004) and male gender (P less than 0.01). Patients who received radiation therapy fared better than those for whom radiation was not given (disease-free survival at 2 years 53% versus 29%). The authors conclude that CNP signifies an aggressive or advanced disease requiring intensive systemic chemotherapy and that the role of irradiation should be examined for this group of patients.

Child↗
PubMed1991

New recurring chromosomal translocations in childhood acute lymphoblastic leukemia.

We identified seven new recurring translocations among 483 cases of acute lymphoblastic leukemia (ALL) with adequate chromosome banding studies. Four were apparently balanced [t(1;3)(p34;p21), t(7;9)(p15;p23-p24), t(12;13)(p13;q14), t(17;19)(q22;p13)], while three were unbalanced with the formation of a dicentric chromosome [dic(7;9)(p13;p11), dic(7;12)(p11;p12), and dic(12;17)(p11;p11-p12)]. One translocation was observed in five cases, two in four cases, and the remaining four in two cases each. The modal chromosome numbers in these 21 cases were 45 (n = 11), 46 (n = 8), and 47 (n = 2). Eight of the 11 cases with a dicentric chromosome had a modal number of 45. Only a single translocation was found in 14 cases (67%), representing the sole structural abnormality in six cases. In three of the seven translocation subgroups, the blast cells were consistently of B lineage (pre-B, early pre-B, or both); in all others, they represented both the B and T lineages. The small size of these subgroups prevented definitive clinical correlations, although it may be important that two of the four cases with a t(17;19) and an early pre-B-cell immunophenotype had disseminated intravascular coagulation, an event usually observed in acute promyelocytic leukemia or T-cell ALL. These findings add substantially to the existing list of nonrandom chromosomal translocations in childhood ALL and may help to explain the genetic alterations leading to the loss of normal growth control mechanisms in this disease.

Adolescent↗
PubMed1991

Cholelithiasis after treatment for childhood cancer.

The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8-54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones.

Adolescent↗
PubMed1991

Hypersensitivity reactions to epipodophyllotoxins in children with acute lymphoblastic leukemia.

The incidence, clinical characteristics, and outcome of hypersensitivity reactions to teniposide (VM-26), etoposide (VP-16), or both were determined in 108 children with acute lymphoblastic leukemia (ALL) treated with a contemporary regimen of intensive multiagent chemotherapy. Fifty (46%) of the 108 patients had one or more hypersensitivity reactions. The risk of any child having an initial reaction over the cumulative dose range studied was 52% (95% confidence limits, 41% and 63%) for VM-26, compared with 34% (95% confidence limits, 24% and 44%) for VP-16. The risk of having an initial reaction to VM-26 or VP-16 was clearly related to the cumulative dose. This risk peaked at 1500 to 2000 mg/m2 for VM-26 and at 2000-3000 mg/m2 for VP-16. All reactions were Type 1 reactions according to the Gell and Coombs classification, characterized by urticaria, angioedema, flushing, rashes, or hypotension, and 86% of reactions were of Grade 1 or 2 severity according to standard criteria. There was no evidence of increasing clinical severity on repeated rechallenge with premedication, and no deaths occurred. The findings suggested that hypersensitivity reactions to epipodophyllotoxins in children with ALL are more common than previously reported, but only rarely constitute dose-limiting toxicity.

Adolescent↗
PubMed1991

Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases.

The t(4;11)(q21;q23) chromosomal abnormality was identified in 40 (2%) of 1,986 children with newly diagnosed acute lymphoblastic leukemia (ALL). This translocation was associated with female sex (63%), age less than 1 year (60%), hyperleukocytosis (median leukocyte count, 156.5 x 10(9)/L), CD10-/CD19+ B-precursor cell immunophenotype, and myeloid-associated antigen (CD15) expression (63%). Nearly all cases had at least some CD24- blast cells. The CD10-/CD15%/CD19+/CD24/+ phenotype was found in 20 of the 32 t(4;11) cases tested. None of the 40 cases had the cytogenetic finding of hyperdiploidy greater than 50, which is a favorable prognostic feature. For clinical comparison, the t(4;11) cases were divided into three groups according to age at diagnosis: less than 1 year (n = 24), 1 to 9 years (n = 8), and greater than or equal to 10 years (n = 8). Compared with older patients, infants were more likely to have initial central nervous system leukemia (P = .05) and less likely to have pre-B-cell ALL (P = .05). Complete continuous remission has been maintained in only 7 of 24 infants and 2 of 8 patients aged greater than or equal to 10 years, in contrast to 7 of 8 children in the intermediate age group (P = .048). These findings suggest that the t(4;11) is an adverse prognostic feature in these two age groups.

Adolescent↗
PubMed1991

Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy.

To improve outcome in childhood acute lymphoblastic leukaemia (ALL), a stratified, randomised study of extended intensified chemotherapy was done. 358 evaluable patients received remission reinforcement therapy (teniposide, cytarabine, high-dose methotrexate) added to a four-drug induction regimen. Those achieving complete remission were randomised on the basis of risk group assignment to conventional continuation treatment or to four pairs of drugs rotated weekly or every 6 weeks. All patients received intrathecal chemotherapy; higher-risk patients also received 1800 cGy cranial irradiation after 1 year of remission. Complete remission was induced in 96% of the patients. At median follow-up of 40 (range 19-73) months, 4-year event-free survival (SE) was 73 (4)% overall, 81 (6)% in the lower-risk group (n = 110), and 69 (5)% in the higher-risk group (n = 248). Outcome within risk groups was not significantly affected by the speed of rotation of drug pairs during continuation treatment. Various high-risk subgroups had apparently improved responses to this treatment. This intensified chemotherapy may cure 69-77% of children with ALL.

Actuarial Analysis↗
PubMed1991

Somnolence, hypotension, and metabolic acidosis following high-dose teniposide treatment in children with leukemia.

This report describes an unexpected adverse effect in three children receiving teniposide at 3-5 times the conventional dosage (i.e. 200 mg/m2) plus cytarabine as part of continuation therapy for acute lymphocytic leukemia. Pharmacokinetic studies in each patient had demonstrated high teniposide clearances, and thus the increased dosage requirements were necessary to attain plasma concentrations similar to those expected for patients with average drug clearance. At 3-4 h after the beginning of the 4-h simultaneous infusions of teniposide and cytarabine, these patients experienced somnolence, hypotension, and metabolic acidosis. The adverse events were associated with elevated teniposide plasma concentrations during the infusions compared with those in patients receiving similar doses without toxicity, and clinically significant ethanol concentrations, presumably from the teniposide formulation. Blood concentrations of cremophor and histamine, which are also constituents of the teniposide formulation, were not measured. In addition, concomitant therapy with antiemetic agents in patients who may have been mildly volume-depleted due to emesis may also play a contributory role. Prolonging the infusion time for patients receiving teniposide doses above 500 mg/m2 will avoid excessive teniposide and ethanol plasma concentrations and minimize the risk of this potentially serious side effect.

Acidosis↗
PubMed1991

Management of anorectal/perineal infections caused by Pseudomonas aeruginosa in children with malignant diseases.

The role of operation for anorectal infections associated with perineal gangrene and cellulitis in children with myelo-suppression from cancer chemotherapy is unclear. We evaluated anorectal/perineal infections caused by Pseudomonas aeruginosa in 16 children with malignant diseases seen over 27 years. In 12 of 16 patients, leukemia was the underlying malignancy (ALL 10, AML 2), and in 13 of 16, severe neutropenia (absolute neutrophil count less than 500/mm3) was present at diagnosis. Cultures of the lesions showed multiple organisms in 14 of 16 patients with Escherichia coli, Klebsiella species, and Enterococcus being the most frequent coexisting organisms. All positive blood cultures grew P aeruginosa exclusively. Of three patients with necrotizing infections, two had complete resolution with medical treatment alone; the other patient who developed this problem while on terminal care died. In none of the 16 patients was a major operation (debridement or diversion) performed. Five patients died, three of whom were considered terminally ill when the anorectal infections occurred. Four of the five deaths occurred before 1974. Since then, only 1 of 7 patients died. Excluding the three terminally ill patients, the success rate of medical therapy alone is 85% (11/13). The antibiotic regimen should include an aminoglycoside in synergistic combination with anti-Pseudomonas penicillin. These results suggest that operative management may have no role in the management of anorectal infections caused by P aeruginosa in children with cancer.

Administration, Topical↗
PubMed1991

Clinical significance of histology and immunophenotype in childhood diffuse large cell lymphoma.

To correlate the histologic subtype of diffuse large cell (DLC) lymphoma with immunophenotype, clinical features, and treatment outcome, 88 consecutively diagnosed children with this disease were studied. Of these cases, 42 (48%) were immunoblastic (IB), polymorphous subtype; 17 (19%) IB, plasmacytoid; 8 (9%) IB, clear cell; 6 (7%) IB, not otherwise specified; and 15 (17%) DLC-follicular center cell (DLC-FCC) type. Of 34 cases successfully phenotyped from paraffin sections, 13 were T cell and 9 were B cell; of the remaining cases, 8 were suggestive of T-cell lineage, 3 of B-cell lineage, and 1 of histiocytic differentiation. Although histologic subtype did not correlate with clinical features or outcome, it did correlate with immunophenotype among those cases for which lineage could be unequivocally assigned (5 of 18 IB vs. 4 of 4 DLC cases were B cell; P = 0.02) Immunophenotype was also correlated with stage of disease (11 of 13 T-cell vs. 3 of 9 B-cell cases had stage III-IV disease; P = 0.03). (Stage III includes all primary thoracic tumors; stage IV includes all with central nervous system and/or bone marrow involvement.) Significant prognostic features were clinical stage and era (thus type) of therapy (P less than 0.001). The authors conclude that most cases of large cell non-Hodgkin's lymphoma in children are of IB morphologic type, most frequently of T-cell lineage, and those with T-cell phenotype appeared to have more advanced disease.

Adolescent↗
PubMed1991

Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X.

We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure.

Adolescent↗
PubMed1991

Childhood acute leukemia with t(11;19) (q23;p13).

From 583 cases of acute lymphoblastic leukemia (ALL) and 181 cases of acute myeloid leukemia (AML) in childhood, seven patients were identified to have t(11;19) (q23;p13) by sequential cytogenetic analyses. The t(11;19) was associated with B-precursor ALL at diagnosis in three patients and at relapse in one patient. All four tested patients with B-precursor failed to express the CD10 antigen when the t(11;19) was detected, and one of three patients tested expressed myeloid-associated markers. In three other patients the translocation was detected either at lineage conversion from ALL to M5 AML (n = 2) or from AML to CD10- B-precursor ALL (n = 1). Leukemic blasts of four patients had an entirely different karyotype at the time of lineage conversion or loss of CD10 expression, suggesting an induction of a second neoplasm. Thus the t(11;19) can be found in de novo or secondary acute leukemia with lymphoid (CD10-) or myeloid (monoblastic) phenotype. Further investigation of the gene(s) involved in the 11q23 chromosomal region and the breakpoints in the 19p13 region is needed to understand the leukemogenesis of this apparently heterogeneous group of disorders.

Adolescent↗