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W Crist

Publications and source records attributed to W Crist.

At least 19 recordsLinked to original sources
PubMed2001

Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: an intergroup rhabdomyosarcoma study.

PURPOSE: To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m(2) of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m(2), dactinomycin 1.5 mg/m(2), and cyclophosphamide 2.2 g/m(2) (VAC) and vincristine 1.5 mg/m(2), topotecan 0.75 mg/m(2) daily x 5, and cyclophosphamide 250 mg/m(2) daily x 5. Patients who did not respond to topotecan received continuation therapy with VAC alone. RESULTS: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P: = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival. CONCLUSION: The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.

Adolescent↗
PubMed2001

Efficacy of ifosfamide and doxorubicin given as a phase II "window" in children with newly diagnosed metastatic rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: The cure rate for children/adolescents with localized rhabdomyosarcoma (RMS) has tripled over the past 25 years, but patients with metastatic disease at presentation have not benefited similarly, and urgently need new therapy. We evaluated a new drug pair, ifosfamide + doxorubicin, for such patients. PROCEDURE: We estimated the complete and partial response rates (i.e., CR and PR) of 152 previously untreated children/adolescents with metastatic RMS entered on the IRS-IV pilot from July 1988 to October 1991 who received an "up-front window" of ifosfamide (1.8 gm/m(2)/day for 5 days) and doxorubicin (30 mg/m(2)/day for 2 days) given every 3 weeks for 12 weeks. This was followed by combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide (VAC), given every 3 weeks for an additional 36 weeks. RESULTS: Of 115 patients evaluable for early response at 12 weeks, 28 (20%) had CR and 66 (43%) had PR. The ultimate CR rate was 52%. Overall, about one-third of patients survived. Prognostic factor analysis revealed that patients < 10 years old (P < 0.001), those with embryonal tumors (P = 0.002), or a GU primary site (P = 0.010), and those who lacked nodal disease (P = 0.041), and those who lacked bone or bone marrow metastasis (P < 0.001) fared better than did others. CONCLUSIONS: The 63% CR + PR rate achieved at 12 weeks and overall 5-year FFS seen with this drug pair is similar to that achieved with previously evaluated drug combinations. We conclude that ifosfamide/doxorubicin is highly active in advanced RMS, and should be considered for inclusion in frontline therapy for children with intermediate or high-risk RMS.

Adolescent↗
PubMed2001

Mealtime behaviors of young children: a comparison of normative and clinical data.

The objective of this study was to compare the behavior of healthy young children around feeding and mealtimes to the behavior of two clinical groups, children referred for feeding problems without related medical issues and those with medical issues associated with the feeding problems. Using the Behavioral Pediatrics Feeding Assessment Scale, data were obtained for 96 healthy children between the ages of 9 months and 7 years, and descriptive information is presented in the paper on these normal mealtime behaviors. In comparing this normative data to similar data obtained from the clinical groups, our primary purpose was to investigate whether children with feeding problems engage in fundamentally different behaviors (maladaptive) or similar behaviors, but at an increased frequency to normal children. Factor analysis identified five common patterns of behavior across the three groups. The difference in parental report of feeding difficulties between healthy and clinical groups appears to reflect the frequency in which the child with feeding difficulties engages in the problematic behavior, rather than fundamental differences in behaviors exhibited during mealtimes.

Child↗
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

Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991.

PURPOSE: One hundred thirty of 2,792 patients (5%) registered on three Intergroup Rhabdomyosarcoma Study clinical trials (IRS-I, -II, and -III) from 1972 to 1991 had an extraosseous Ewing's sarcoma (EOE). We report here the results of multimodality therapy for this tumor. PATIENTS AND METHODS: The 130 patients were less than 21 years of age; 70 (54%) were males. Primary tumor sites were on the trunk in 41 patients, an extremity in 34, the head/neck in 23, the retroperitoneum/pelvis in 21, and other sites in 11. One hundred fourteen patients had no metastases at diagnosis. In 21 patients, the tumor was completely resected; in 30, the localized or regional tumor was grossly resected, and in 63 patients, grossly visible sarcoma was left behind. Sixteen patients (12%) had distant metastases at diagnosis. All patients were given multiagent chemotherapy and most received irradiation (XRT); none were treated with bone marrow transplantation. RESULTS: One hundred seven patients (82%) achieved a complete response. At 10 years, 62%, 61%, and 77% of the patients were alive after treatment on IRS-I, IRS-II, or IRS-III therapeutic protocols, respectively, similar to figures obtained in all IRS patients. At last follow-up evaluation, 42 patients had died of progressive tumor and one of infection. Survival at 10 years was most likely for patients with tumor that arose in the head and neck, extremities, and trunk, and for those who underwent grossly complete tumor removal before initiation of chemotherapy. For patients with localized, gross residual tumor, adding doxorubicin (DOX) to the combination of vincristine, dactinomycin, cyclophosphamide (VAC), and XRT did not significantly improve survival in 39 patients (62% alive at 10 years) compared with that of 24 patients treated with VAC and XRT without DOX (65% alive at 10 years, P = .93). CONCLUSION: This series indicated that EOE in children is similar to rhabdomyosarcoma (RMS) in its response to multimodal treatment. No benefit was apparent from the addition of DOX to VAC chemotherapy in patients with gross residual EOE.

Adolescent↗
PubMed1996

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

Adolescent↗
PubMed1995

The Third Intergroup Rhabdomyosarcoma Study.

PURPOSE: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. PATIENTS AND METHODS: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). RESULTS: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS estimates, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. CONCLUSION: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.

Adolescent↗
PubMed1994

Retroperitoneal node biopsy in paratesticular rhabdomyosarcoma.

UNLABELLED: Retroperitoneal lymph node dissection (RPLND) was used in 121 Intergroup Rhabdomyosarcoma Study (IRS) III patients with nonmetastatic paratesticular (PT) rhabdomyosarcoma (RMS) to assess retroperitoneal lymph node (RPLN) involvement so as to determine the need for x-ray therapy (XRT). Clinical node evaluation (CNE) was accomplished by a computed tomography (CT) scan in 105 and a sonogram in six. Pathological node evaluation (PNE) was performed in 113: lymphadenectomy (9 bilateral, 85 unilateral) and biopsy in 19. Vincristine and actinomycin D were used for 1 year postoperatively in 89%; all patients who had positive PNE received RPLN XRT. This study compares CNE with PNE and evaluates predictors of relapse and survival. FINDINGS: There were clinically negative nodes (cN0) in 81% of the 121 patients. Among cN0 patients, 14% had positive nodes (pN1). Of the clinically positive (cN1) patients, 94% had pN1. RPLN relapse occurred in only two of the 121 patients. Initially both had cN0 and one had PNE that was negative. For all 121 patients, the 5-year survival was 91%. For cN0 patients, the 5-year survival was 96% compared with 69% for cN1 patients (P < .001). Among the children in whom treatment failed, nodes were cN1 in 5 of 11 (45%) compared with 15 of 107 (14%) in those whose treatment did not fail (P < .008). CONCLUSIONS: (1) Results of RPLN imaging studies were negative in 81% of patients with PT RMS (specificity 99%, sensitivity 57%). (2) RPLN recurrence is uncommon (even when RPLN are initially involved) if regional XRT and appropriate chemotherapy are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Phase I study of oral etoposide in children with refractory solid tumors.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and plasma concentrations of orally administered etoposide (VP-16) in pediatric oncology patients. PATIENTS AND METHODS: In a phase I study, 20 children with refractory solid tumors received oral VP-16 (the intravenous preparation diluted with sodium chloride) three times daily for 21 days. Daily dose levels studied were 50 mg/m2 (n = 5), 60 mg/m2 (n = 7), and 75 mg/m2 (n = 8). VP-16 concentrations were measured in blood samples collected on days 1, 7, 14, and 21. RESULTS: Grade 3 to 4 thrombocytopenia and/or neutropenia causing interruption of the 21-day course or persisting for more than 7 days after the last day of chemotherapy was seen at all dose levels, but was not dose-limiting. One patient treated at the 50-mg/m2 daily dose died of sepsis. At the 75-mg/m2 dose level, diarrhea was dose-limiting. Estimated plasma VP-16 concentrations were greater than 1 micrograms/mL for median periods of 9.4, 15.4, and 13.5 hours per day at daily doses of 50, 60, and 75 mg/m2, respectively. Responses were observed in seven of 14 patients who received at least one additional course of etoposide after a rest period of 7 days. There was one complete and two objective responses. Four patients were considered to have stable disease. CONCLUSION: The intravenous preparation of VP-16 administered orally appears to be well tolerated by heavily pretreated pediatric patients. On the three-times daily, 21-day schedule, a daily dose of 75 mg/m2 exceeds the MTD, with diarrhea as the dose-limiting toxicity. The recommended dose for oral etoposide is 60 mg/m2/d administered every 8 hours.

Administration, Oral↗
PubMed1993

The Intergroup Rhabdomyosarcoma Study-II.

BACKGROUND: Intergroup Rhabdomyosarcoma Study (IRS)-II, (1978-1984) had the general goals of improving the survival and treatment of children with rhabdomyosarcoma (RMS). METHODS: Nine hundred ninety-nine previously untreated eligible patients entered the study after surgery and were randomized or assigned to therapy by IRS Clinical Group (I-IV), tumor site, and histologic type. Outcomes were compared between treatments and with results of IRS-I (1972-1978). RESULTS: Patients in Group I, excluding extremity alveolar (EA) RMS, were randomized to standard vincristine (V), dactinomycin (A), and cyclophosphamide (C) or standard VA. At 5 years, disease-free survival (DFS) and survival (S) rates were similar between VAC and VA (DFS: 80%, 70%, P = 0.47; S: 85%, 84%, P = 0.73). Patients in Group II, excluding EA RMS, received radiation and were randomized to intensive VA or repetitive-pulse VAC. Outcomes were similar for rates of DFS (69%, 74%, P = 0.83) and S (88%, 79%, P = 0.17). Patients in Group III, excluding certain pelvic tumors, received radiation and were randomized to repetitive-pulse VAC or repetitive-pulse VAdrC-VAC (Adr, Adriamycin [doxorubicin]). Complete remission (CR) rates were close at 74%, 78%, respectively (P = 0.32), as were percentages in CR (73%) and S (66%) rates; the latter outcomes were significantly better than IRS-I (CR: 56%, P < 0.001; S: 50%, P < 0.001). Central nervous system prophylaxis for Group III patients with cranial parameningeal sarcoma increased S rate to 67% from 45% in IRS-I (P < 0.001). Patients in Group IV received the same regimens as Group III; the CR rate was 53%, 38% remained in CR and S rate was 27% with and 26% without Adr (P = 0.90). At 5 years, S rate for IRS-II, including EA and all pelvic tumors, was 63%: an 8% increase over IRS-I (P < 0.001). Outcomes by primary site were as good as, or better than, the IRS-I experience. CONCLUSIONS: Combining all Groups and treatments in IRS-II, the major improvement in S rate at 5 years between studies was in nonmetastatic patients (71% for IRS-II versus 63% for IRS-I, P = 0.01).

Adolescent↗
PubMed1993

Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS: With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS: The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION: TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Transitional pre-B-cell acute lymphoblastic leukemia of childhood is associated with favorable prognostic clinical features and an excellent outcome: a Pediatric Oncology Group study.

The presenting characteristics and survival of children with the newly recognized transitional cell pre-B immunophenotype of acute lymphoblastic leukemia (ALL) are compared with those of children with pre-B ALL to determine the clinical significance of the new phenotype. Patients with transitional pre-B ALL (n = 17), defined by lymphoblasts expressing cytoplasmic and surface mu heavy chains without kappa or lambda light chains, have lower initial leukocyte counts (p = 0.02) and a higher frequency of DNA indexes > 1.16 (p < 0.001) than patients with pre-B ALL (n = 501), whether or not cases with the unfavorable prognostic (1;19) translocation are included in the analysis. Patients with transitional pre-B ALL lack FAB L3 morphology, bulky extramedullary disease, surface kappa or lambda chains, and the (8;14), (8;22), and (2;8) translocations, features that characterize the syndrome of B-cell ALL. The 4-year relapse-free survival result for children with transitional pre-B ALL appears better than that for children with pre-B ALL (93.3 +/- 17% versus 72.9% +/- 4.6%), but this difference is not statistically significant. We conclude that patients with transitional pre-B ALL have a very favorable prognosis in the context of the therapy used in this study.

Adolescent↗
PubMed1992

G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T cells.

A highly purified, 300-Kd bispecific monoclonal antibody (MoAb) heteroconjugate was prepared by covalently linking the anti-CD3 MoAb, G19.4, to the anti-CD19 MoAb, B43. Dual-color staining techniques and multiparameter flow cytometry confirmed that this alpha CD3 x alpha CD19 heteroconjugate was able to bind to both CD3+ T cells and CD19+ t(4;11) acute lymphoblastic leukemia (ALL) cells. T-cell-mediated lysis of freshly isolated primary bone marrow blasts from nine newly diagnosed ALL patients with a t(4;11)(q21;q23) chromosomal translocation were studied with 51Cr-release assays. Picomolar concentrations of alpha CD3 x alpha CD19 MoAb heteroconjugate effectively triggered lysis of CD19+ t(4;11) ALL cells by interleukin-2-activated CD3+ peripheral blood T-cell (PBTC) effectors but did not augment the cytolytic activity of the same effectors against CD19- T-ALL cells. In contrast to the alpha CD3 x alpha CD19 heteroconjugate, neither the alpha CD3 x alpha CD3 homoconjugate control nor the alpha CD19 x alpha CD72 heteroconjugate control facilitated the cytolysis of t(4;11) ALL blasts. Occupation of the target CD19 binding sites on t(4;11) ALL blasts by preincubation with excess unconjugated alpha CD19 MoAb abrogated the potentiating effects of the alpha CD3 x alpha CD19 heteroconjugate on PBTC-mediated cytolysis. Thus, the cell type-specific cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19 heteroconjugate. To our knowledge, this is the first description of an effective bispecific antibody that facilitates the T-cell-mediated lysis of t(4;11) ALL blasts.

Antibodies, Monoclonal↗
PubMed1992

Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study.

PURPOSE: Using the technique of recursive partitioning and amalgamation analysis with verification, the Pediatric Oncology Group (POG) investigated the independent prognostic significance of previously published prognostic factors significantly associated with event-free survival (EFS) in B-progenitor cell acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Age, leukocyte count, sex, immunophenotype (expression of cytoplasmic immunoglobulin [Ig] and of surface antigens CD10 and CD34), and DNA index (ratio of the flow cytometry-determined DNA content of leukemia cells to that of normal diploid cells) were the variables used in the evaluation of four antimetabolite-based chemotherapy regimens in 1,535 children with the newly diagnosed B-progenitor cell ALL between February 1986 and May 1990. RESULTS: There were three subgroups at widely different risks of treatment failure. A DNA index greater than 1.16 was the most prognostic feature. The final prognostic subgrouping was as follows: (1) DNA index greater than 1.16; (2) DNA index less than or equal to 1.16, age less than 11.0 years, and leukocyte count less than 50 x 10(9)/L; and (3) DNA index less than or equal to 1.16, (age greater than 11.0 years, and/or leukocyte count greater than 50 x 10(9)/L). These groups made up 20%, 53%, and 27% of the patients and had 4-year EFS rates (SE) of 90.1% (6.3%), 80.5% (5.1%), and 50.4% (7.6%), respectively. CONCLUSIONS: Use of the DNA index, leukocyte count, and age--data that are relatively inexpensive and simple to obtain--may be sufficient to stratify patients with B-progenitor cell ALL for risk-directed therapy. Patients at an extremely low risk of failing therapy (approximately 20% of cases in this study) can thus be identified and spared the toxic short-term and late effects of more intensive therapies that may be needed for children with less favorable clinical and biologic features.

Adolescent↗
PubMed1992

Current results of studies of immunophenotype-, age- and leukocyte-based therapy for children with acute lymphoblastic leukemia. The Pediatric Oncology Group.

From February 1986 to January 1991 the Pediatric Oncology Group (POG) treated 2404 children or adolescents with acute lymphoblastic leukemia (ALL) on immunophenotype (T-, B-, Pre-B, or Early pre-B-cell), age, and leukocyte count based treatment protocols (ALinC 14, T-cell 3, B-cell and infant leukemia studies). The immunophenotypic subgroups comprised 78.9% B-precursor cell, 15.1% T-cell, 2.0% B-cell, and 4% infant ALL. Patients with B-progenitor cell ALL were stratified by age and leukocyte count and randomized to receive induction therapy comprised of vincristine, prednisone, and asparaginase with triple intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine), followed by intensification with moderate-dose MTX (Regimen A), moderate-dose MTX plus asparaginase (Regimen B), moderate-dose MTX plus cytarabine given early (Regimen C), or moderate-dose MTX plus cytarabine given over the first 16 months of therapy (Regimen D). Continuation therapy comprised mercaptopurine and methotrexate with vincristine plus prednisone pulses. Central nervous system preventive treatment was continued for two years. Patients with T-cell or B-cell ALL or infants less than 1 yr old were treated on individual very intensive multiagent therapy protocols. The 4-year event-free survival for all patients was 66.4% +/- 2.4%; B-precursor ALL approximately 72%, T-ALL approximately 50%, B-ALL approximately 60%, and infants less than 1 yr old approximately 16.5%. We conclude that about two-thirds of newly diagnosed children with ALL can be cured with this approach which spares the majority of children exposure to alkylating agents, anthracyclines, epipodophylotoxins, and irradiation, diminishing the risks of serious acute and late effects.

Adolescent↗
PubMed1992

The non-random dic(9;12) translocation in acute lymphoblastic leukemia is associated with B-progenitor phenotype and an excellent prognosis.

A dicentric translocation involving the short arms (p) of chromosomes 9 and 12 was identified in 15 of 2303 successfully banded cases of acute lymphoblastic leukemia (ALL) in children, consecutively entered on protocols of the Pediatric Oncology Group (1986-1990) or St Jude Children's Research Hospital (1984 and 1990). The dic(9;12)(p1?1;p1?2) was seen only in patients with a B progenitor cell immunophenotype: the frequency was 0.8% among pre-B cases (4/508) and 0.9% (11/1177) among early pre-B cases. Laboratory and clinical characteristics were similar to those of the general population of children with ALL, with the exception of a marked male preponderance (12/15 cases). Flow cytometric studies revealed a leukemic cell DNA index of 1.0 in all cases. All fifteen patients are in continuous complete remission at a median follow-up duration of 57+ months (range 9-93+ months). These findings suggest that the dic(9;12) is a recurrent chromosomal translocation in pediatric ALL, occurs exclusively in B-progenitor ALL, and unlike other non-random translocations, is associated with an excellent prognosis.

Adolescent↗
PubMed1991

Philadelphia chromosome and monosomy 7 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.

During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial or complete monosomy 7 (-7). This subgroup of children with Ph1/-7 ALL was comprised primarily of older males with early B-lineage ALL. Bone marrow specimens from six Ph1/-7 patients were studied further using the polymerase chain reaction and primers that flank the ALL, and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9;22 translocation. Rearrangements were detected in RNA from bone marrow and/or peripheral blood cells of six patients, although four were in hematologic remission at the time of the analysis. Five cases showed the ALL breakpoint, while one child with Ph1/-7 showed the chronic myelogenous leukemia breakpoint. The induction failure rate was much higher in this subgroup (31%) as compared with Ph1-negative cases, and the projected duration of event-free survival reflected the aggressive nature of this subgroup because no children are projected to remain in remission at 2 years. ALL with both the 9;22 translocation and -7 appears to represent a unique and previously undescribed subgroup of childhood ALL associated with a particularly adverse outcome. Leukemic transformation in such patients may involve the interaction of a dominant oncogene (Ph1) and a tumor suppressor gene (-7).

Adolescent↗