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Biomedical subjects

H Mahmoud

Publications and source records attributed to H Mahmoud.

At least 37 records · Page 2Linked to original sources
PubMed1995

Tumor lysis syndrome: pathogenesis and management.

Tumor lysis syndrome refers to the metabolic disturbances (hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia) associated with lymphoproliferative malignancies which occur secondary to cell lysis. In some patients, tumor lysis results in acute renal failure. The nature and severity of the metabolic alterations are variable and may be influenced by the timing and intensity of chemotherapy, the magnitude of cell lysis, and the general condition of the patient with respect to hydration and glomerular filtration rate. Not only do hyperuricemia and hyperphosphatemia result from tumor lysis syndrome, they also contribute to oliguric acute renal failure in patients with tumor lysis. The pathogenesis of tumor lysis syndrome and current therapeutic strategies are discussed.

Acute Kidney Injury↗
PubMed1995

An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia.

PURPOSE: To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse during first remission of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a median age of 7 years. Five had CNS leukemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and the remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five-agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered weekly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation (cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was administered. RESULTS: All 20 children achieved a second complete remission. The 5-year estimate of disease-free survival (mean +/- SE) was 70% +/- 11%. Thirteen patients remain in remission at 71+ to 126+ months (median, 104+), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 patients, remained in second remission. CONCLUSION: This intensive retrieval therapy is effective and well tolerated by children with an isolated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologic impairment.

Adolescent↗
PubMed1994

Clinicopathologic features and treatment outcome of children with large-cell lymphoma and the t(2;5)(p23;q35).

The t(2;5)(p23;q35) was detected in 9 of the 18 cases of large-cell lymphoma with an abnormal karyotype among 115 children with large-cell lymphoma treated at St Jude Children's Research Hospital from 1975 to 1993. When the cases containing the t(2;5) were classified according to the National Cancer Institute Working Formulation, 7 were large-cell, immunoblastic and 2 were diffuse large cell; according to the Kiel classification system, 6 were anaplastic large cell, 2 immunoblastic, and 1 centroblastic. CD30 expression was documented in 6 of 8 cases tested. All patients had nodal disease and 6 had extranodal involvement (bone in 4 cases and skin in 3). Eight of nine had advanced disease at diagnosis (stage Ill in 7 and stage IV in 1). Complete remission (CR) was attained in all patients and 6 remain in first CR for 19+ to 97+ months. Three relapsed, but successfully obtained second remissions; 2 are 58+ and 80+ months after retrieval therapy for local recurrences, and 1 patient died of recurrent disease. The t(2;5)(p23;q35) is associated with, but not limited to, anaplastic histology, a CD30+ T-cell phenotype, advanced stage disease with nodal (+/- extranodal) involvement, and chemosensitivity at diagnosis and relapse.

Adolescent↗
PubMed1994

Pulmonary insufficiency complicating therapy with high dose cytosine arabinoside in five pediatric patients with relapsed acute myelogenous leukemia.

BACKGROUND: The occurrence of fatal or nearly fatal pulmonary insufficiency in 5 of 22 pediatric patients with relapsed acute myelogenous leukemia (AML) treated with high dose cytosine arabinoside (Ara-C) at St. Jude Children's Research Hospital, Memphis, Tennessee, and institutions affiliated with the Pediatric Oncology Group (POG) is reported. METHODS: Cytosine arabinoside (1.0-1.5 g/m2/day) was given as a 5-day continuous infusion to all patients. Four patients with persistent leukemia received a second 3- or 5-day course. The POG protocol included the administration of granulocyte colony stimulating factor for the priming of myeloblasts. Diagnostic criteria for pulmonary insufficiency included noncardiogenic pulmonary edema with exclusion of underlying cardiorespiratory, infectious, or metabolic conditions. Autopsy material also was reviewed. RESULTS: Of the 22 patients 5 died (23%), including 2 who received a second course of Ara-C as a result of pulmonary insufficiency that developed at a median of 8 days (range, 3-38 days) after the first course. Three patients died despite intubation and pressor support. Two patients were managed successfully with colloids, diuresis, and oxygen by face mask; remission was achieved in both. The postmortem examination of one patient disclosed airless lungs, profound pulmonary edema, and subpleural nodules, but no evidence of leukemia. CONCLUSION: Pulmonary insufficiency from high dose Ara-C varies in severity and may be fatal. It may occur during or after treatment. Awareness of this potential complication, careful attention to fluid status, and aggressive supportive care may optimize outcome.

Acute Disease↗
PubMed1994

Complete hematologic remissions induced by 2-chlorodeoxyadenosine in children with newly diagnosed acute myeloid leukemia.

The majority of children with acute myeloid leukemia (AML) who are treated exclusively with chemotherapy die of progressive disease. Improvement in outcome will likely require new active drugs capable of eradicating resistant blast cells early in the clinical course. We therefore assessed the cytoreductive potential of 2-chlorodeoxyadenosine (2-CdA), a halogenated purine analogue, in 22 consecutive children with newly diagnosed AML. The drug was administered as a single 120-hour continuous infusion (8.9 mg/m2 of body surface area per day) before the introduction of standard remission induction therapy. Six patients (27%) had complete hematologic remissions by a median of 21 days after treatment with the nucleoside (range, 14 to 33 days). Seven others had partial responses, yielding a total response rate of 59%. The drug also eliminated leukemic cells from cerebrospinal fluid in 4 of the 6 patients tested. Concentrations of 2-CdA in cerebrospinal fluid on day 5 after the initiation of treatment ranged from 12.4% to 38.0% (mean, 22.7%) of the steady-state plasma concentrations. Severe but reversible myelosuppression and thrombocytopenia developed in all patients. Analysis of factors that may have influenced the complete remission rate suggested a better outcome in patients with myeloblastic leukemia (M0-M2 subtypes in the revised French-American-British classification system). These results demonstrate clinically significant activity by 2-CdA against previously untreated AML in children, including leukemic blast cells in the central nervous system. Its use in combination chemotherapy may improve the outlook for patients with this often fatal hematologic cancer.

Adolescent↗
PubMed1994

Factors contributing to the prognostic significance of bone marrow involvement in childhood non-Hodgkin lymphoma.

To evaluate the clinical characteristics and treatment outcome of childhood non-Hodgkin lymphoma (NHL) cases with bone marrow involvement, we studied 13 lymphoblastic, 15 small noncleaved cell, and 8 large cell cases with tumor cells in their marrow. They represented 16%, 11%, and 9% of consecutive NHL cases with these respective histologic subtypes. The treatment outcome differed significantly according to histologic subtype--the 5-year event-free survivals (EFS +/- SE) for large cell NHL, small non-cleaved cell NHL, and lymphoblastic NHL cases were 11 +/- 8%, 40 +/- 20%, and 62 +/- 15%, respectively. Increased serum lactate dehydrogenase (LDH) levels (> 500 U/L) were associated with a poorer EFS (5-year EFS, 0% vs. 50 +/- 10%; P < 0.001). Children < or = 5 years of age had a poorer EFS survival than older children (5-year EFS, 14 +/- 9% vs. 44 +/- 10%; P = 0.03). The degree of bone marrow involvement (< 5% vs. > or = 5%) and race were not significantly associated with treatment outcome. Although intensive chemotherapy has substantially improved survival for patients with advanced stage lymphoblastic or small noncleaved cell lymphoma, patients with large cell NHL and associated marrow involvement continue to have a dismal outcome and require novel or more intensive therapy.

Adolescent↗
PubMed1994

Pharmacokinetics of vincristine in children and adolescents with acute lymphocytic leukemia.

We studied the pharmacokinetics of vincristine in children with acute lymphocytic leukemia by means of a specific high-performance liquid chromatographic assay with ultraviolet and electrochemical detection and a limited sampling strategy. Our objectives were to characterize the disposition of vincristine in pediatric patients, to determine clinical, demographic, or biochemical variables related to variability in vincristine pharmacokinetic parameters, and to assess the relationship between pharmacokinetic parameters and vincristine neurotoxicity. Plasma samples were collected at 5 and 30 minutes, and 1, 3, and 24 hours after a rapid intravenous injection during 3 minutes. Vincristine-induced neurotoxicity was retrospectively evaluated by chart review. Pharmacokinetic studies were completed for 64 doses in 54 children between 2 months and 18 years of age (median, 4.3 years), including 2-month-old monozygous twin girls. Vincristine clearance, estimated by Bayesian methods, was highly variable, with a mean (SD) clearance of 19.9 (14.9) ml/min per kilogram or 482 (342) ml/min per square meter. Mean clearance for all subjects was faster than in published studies of adults, which may be related in part to the greater specificity of the assay used in our study, as well as to age-related differences in drug disposition. Vincristine-associated neurotoxicity was frequent but mild and was not predicted by vincristine systemic exposure; however, neurotoxicity may have been underestimated. Clearance in one patient who received concomitant treatment with pentobarbital exceeded the 75th percentile for all patients, and four of five patients receiving concomitant histamine2 antagonists had clearances below the 25th percentile for all subjects, suggesting that drugs that induce or inhibit hepatic cytochrome P-450 enzymes may affect vincristine disposition. Further studies are needed to identify the factors responsible for interpatient variability in vincristine disposition and to develop improved dosing guidelines.

Adolescent↗
PubMed1994

Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia.

High-dose methotrexate (HDMTX) is a component of most treatment protocols for childhood acute lymphoblastic leukemia (ALL), yet recent studies of receptor-mediated transport and saturable polyglutamylation have questioned its rationale. To investigate this in vivo, methotrexate and its active polyglutamated metabolites (MTX-PG) were measured in bone marrow blasts obtained from 101 children randomized to single-agent therapy with either HDMTX (1 g/m2 per 24 h i.v., n = 47) or low-dose MTX (LDMTX, 30 mg/m2 by mouth every 6 h x 6, n = 54), before remission induction therapy. Blast concentrations of total MTX-PGs (median 460 vs 1380 pmol/10(9) cells) and of long-chain MTX-glu4-6 were both significantly higher after HDMTX (P < 0.001). With either treatment, MTX-PGs were significantly higher in B-lineage blasts than in T-lineage blasts (LDMTX P = 0.001, HDMTX P = 0.03). In a multiple regression analysis of B-lineage ALL, blast MTX-PG was significantly related to MTX dose (or plasma MTX concentration), lymphoblast ploidy (hyperdiploid > nonhyperdiploid), and percentage S-phase. This is the first evidence that HDMTX achieves higher MTX-PG concentrations in ALL blasts in vivo, establishing a rationale for HDMTX in the treatment of childhood ALL, especially T-lineage or nonhyperdiploid B-lineage ALL, disease characteristics associated with a poor prognosis on conventional therapy.

Adolescent↗
PubMed1994

Clinical features and treatment outcome for children with CD30+ large-cell non-Hodgkin's lymphoma.

PURPOSE: To determine the frequency of CD30 expression and its relationship to clinical features, immunophenotype, histotype, and outcome in childhood large-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: We reviewed 45 cases of large-cell NHL in children treated at St Jude Children's Research Hospital from 1975 to 1990 for whom there was sufficient tissue to perform immunophenotypic studies. All 45 were screened with a panel of antibodies to detect the presence of CD30 and T-cell and B-cell antigens. Cases were classified according to the National Cancer Institute (NCI) Working Formulation and the Kiel classification system. Clinical features, immunophenotype, pathologic classification, and treatment outcome were compared for CD30+ and CD30- cases. RESULTS: CD30 expression was documented in 18 cases (40%). These 13 boys and five girls had a median age of 13 years at diagnosis. Most (n = 14) had advanced-stage (III and IV) disease. Nodal disease was equally common in CD30+ and CD30- cases, whereas skin involvement was significantly more frequent in CD30+ cases (P = .007). There was no significant association of CD30 expression with histologic subtype according to the NCI Working Formulation, but CD30+ cases were more likely to be anaplastic by the Kiel classification (P < .001). All CD30+ cases had either T-cell or null-cell phenotype, while the majority of CD30- cases were B-cell phenotype (P < .001). Among patients with limited-stage disease, the mean +/- SE estimated 5-year event-free survival (EFS) was 75% +/- 22% for CD30+ cases and 92% +/- 9% for CD30- cases (P = .10); estimates for advanced-stage disease were 57% +/- 17% and 29% +/- 17%, respectively (P = .096). For patients with advanced-stage disease, CD30 expression was associated with a significantly better overall 5-year survival probability (84% +/- 12% v 27% +/- 16%, P = .0016). CONCLUSION: CD30 is frequently expressed in pediatric large-cell NHL and is significantly associated with T-cell or null-cell phenotype, anaplastic morphology, skin involvement, and better overall survival among advanced-stage patients.

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↗
PubMed1994

Large cell non-Hodgkin lymphoma of childhood: clinical characteristics and outcome.

Less is known about the clinical features and treatment outcome in pediatric large cell non-Hodgkin lymphoma (NHL) than the lymphoblastic and small noncleaved cell subtypes of NHL. To characterize presenting features and assess possible risk factors associated with this diagnosis, we analyzed data for 91 patients treated on a succession of multiagent regimens from 1975 to 1990. Five-year event-free survival (EFS) (+/- SE) was related to disease extent (St Jude system): stage I (n = 24), 95% +/- 5%; stage II (n = 20), 84% +/- 9%; stage III (n = 38), 50% +/- 10%; and stage IV (n = 9), 22% +/- 11%. Advanced stage disease, age < or = 5 years and serum LDH > 500 U/l were associated with poorer EFS in the univariate model (p < 0.001, 0.005, and 0.002, respectively). In the multivariate model, advanced stage and age retained prognostic significance (p = 0.001 and 0.02, respectively), but LDH did not. Among limited stage cases, age < or = 5 years was the only adverse risk feature (p = 0.016); treatment era (pre- vs. post-1979) was the only significant feature in patients with advanced disease (p = 0.004). Intrathoracic primaries were associated with a better outcome than other sites among the 38 stage III patients (p = 0.005). Only one of eight patients with bone marrow disease remains failure-free. The excellent results for limited stage pediatric large cell NHL permit consideration of treatment modifications to decrease toxicity; for cases with advanced disease, especially those with bone marrow involvement, novel therapeutic approaches are clearly needed.

Adolescent↗
PubMed1993

In utero rearrangements in the trithorax-related oncogene in infant leukaemias.

The majority (approximately 75%) of infant acute leukaemias have a reciprocal translocation between chromosome 11q23 and one of several partner chromosomes. The gene at 11q23 (named MLL, ALL-1, HRX or HTRX-1; refs 2-6) has been cloned and shares homology with the Drosophila developmental gene trithorax. Rearrangements of this gene (called HRX here) occur in introns and cluster in a region of approximately 10 kb; individual patients have different breakpoints. Here we describe three pairs of infant twins with concordant leukaemia who each share unique (clonal) but non-constitutive HRX rearrangements in their leukaemic cells, providing evidence that the leukaemogenic event originates in utero and unequivocal support for the intra-placental 'metastasis' hypothesis for leukaemia concordance in twins.

Chromosomes, Human, Pair 11↗
PubMed1993

Progress in the treatment of adolescents with acute lymphoblastic leukemia.

UNLABELLED: BACKGROUND AND METHODS. The authors studied the clinical and biologic features and treatment response of 358 children with acute lymphoblastic leukemia (ALL), including 90 adolescents, treated on a single multiagent protocol (St. Jude Total Study XI, 1984-1988). This was done to clarify whether the disease differed in adolescents and to determine the degree of improvement in treatment outcome produced by this modern intense chemotherapy. RESULTS: Compared with the younger children (1-9 years of age; infants 1 year old or younger excluded; n = 257), adolescents (10-18 years of age; n = 90) were significantly more likely to have adverse prognostic features, including T-cell phenotype, L2 blast cell morphologic characteristics, blasts with negative findings for common ALL antigen, and ploidy other than hyperdiploidy greater than 50. Eighty-six of the 90 (96%) adolescents achieved a complete remission, a rate similar to that of the children (97%). Although the event-free survival (EFS) of adolescents was shorter than that of younger children (5-year EFS of 66 +/- 8% versus 75 +/- 5%, respectively; P = 0.04), in this analysis of consecutively treated patients with ALL it showed a significant statistical and clinical improvement as compared with that in our previous study (St. Jude Total Study X, 1979-1983; 5-year EFS rate of 66 +/- 8% versus 37 +/- 5%, respectively; P < 0.001). Within the adolescent group treated on Total Study XI, the EFS was worse for those older than 15 years of age than for those 10-14 years old (46 +/- 15% versus 75 +/- 8%, respectively; P = 0.007). Toxic effects primarily included myelosuppression without severe sequelae. Approximately 96% of the therapy was administered in the outpatient setting. CONCLUSIONS: The increased frequency of unfavorable clinical and biologic features undoubtedly accounts for the poorer prognosis of adolescents with ALL, a conclusion supported by the lack of independent prognostic importance of age in this study. The authors conclude that approximately two-thirds of adolescents can be cured when treated with this intensive but tolerable therapy, showing that this form of treatment significantly has changed the prognosis of adolescents with ALL.

Adolescent↗
PubMed1993

Avascular femoral head necrosis in pediatric cancer patients.

Avascular femoral head necrosis was identified in 15 patients treated at a major pediatric oncology center from 1974 to 1991. The predominant underlying diagnosis was acute leukemia (lymphoblastic, n = 6; non-lymphoblastic, n = 2); two patients had chronic myeloid leukemia, two Hodgkin's disease, and three other solid tumors. Patients ranged from 7 to 27 years of age at diagnosis of this complication, with a median interval of 25 months (range, 0-11 years) from primary diagnosis. Both steroids and radiation therapy appear implicated in the pathogenesis of avascular necrosis: nine patients had received high cumulative doses of prednisone (3.4-14 g/m2), four had received 35-64.8 Gy local irradiation involving the femoral head, and one underwent total body irradiation (12 Gy). Of the 11 surviving patients, six are asymptomatic and fully active. Two patients have joint pain that is responsive to conservative measures. Severe pain and joint deterioration necessitated arthroplasty in two cases, and a third child is undergoing orthopedic evaluation because of worsening symptoms. Thus, like adult cancer patients, children who receive high doses of steroids or local irradiation involving femoral heads are at risk for avascular necrosis. In patients with chronic myeloid leukemia, the complication may be disease related. Although outcomes in our series are better than those reported in adults, the long period of risk for these children and young adults precludes definitive conclusions.

Adolescent↗
PubMed1993

Anti-pan T lymphocyte ricin A chain immunotoxin (H65-RTA) and methylprednisolone for acute GVHD prophylaxis following allogeneic BMT from HLA-identical sibling donors.

Six patients (five children < or = 12 years old and one young adult) underwent allogeneic BMT (not T lymphocyte-depleted) from sex-matched HLA-identical siblings. GVHD prophylaxis consisted of methylprednisolone (30 mg/m2) and anti-pan T lymphocyte ricin A chain immunotoxin (H65-RTA) (0.1 mg/kg) administered daily for 12 consecutive doses. H65-RTA was initiated at day +5 (n = 4) or day +2 (n = 2). All patients engrafted. Despite receiving the planned GVHD prophylaxis, all patients developed moderate to severe acute GVHD; five patients developed Grade III/IV GVHD. Four patients died 34 to 78 days post-transplant; GVHD was a contributory cause of death in each case. H65-RTA as used in this study was ineffective for the prophylaxis of acute GVHD.

Adult↗
PubMed1992

Current strategies for treatment of acute myeloid leukemia at St Jude Children's Research Hospital.

We examined the feasibility of maintaining specific plasma concentrations of ara-C and VP-16 in children with AML. Sixty-one children were treated with 6 sequential cycles of intensive chemotherapy consisting of: (1) cytarabine (ara-C)/VP-16, (2) ara-C/daunorubicin (Dauno), (3) VP-16/amsacrine (m-AMSA), (4) VP-16/5-azacytidine (5-Az), (5) ara-C/Dauno, and (6) ara-C/VP-16. Fifty-nine children had de novo AML, and 2 had a previous myelodysplastic syndrome. The number of patients with each specific FAB subtype was: M0-1; M1-7; M2-24; M3-7; M4-5; M5-11; and M7-6. Simultaneous continuous infusions of ara-C and VP-16 (cycle 1) given at individualized doses to achieve drug plasma concentrations of 1 microM and 30 microM, respectively, produced complete remission (CR) in 26 of 61 patients (43%); an additional 17 patients entered CR after Dauno/ara-C (cycle 2), and one patient required 4 cycles of chemotherapy to achieve CR (total CR rate = 72%). The preliminary 2-year event-free survival (EFS) for patients with FAB-M1 and -M2 AML was only 15% versus 40% for those with FAB-M4 and -M5 AML. Overall, 21 of the 61 patients remain in CR (2-yr EFS = 29%). We conclude that intense treatment with ara-C and VP-16 at doses individualized to achieve target plasma concentrations is feasible although severely myelosuppressive. It results in an acceptable CR rate, but does not improve EFS.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Chloroadenosine↗
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↗