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J T Sandlund

Publications and source records attributed to J T Sandlund.

At least 73 records · Page 4Linked to original sources
PubMed1996

Sweet syndrome in a patient with osteosarcoma.

Neutrophilic dermatosis (Sweet syndrome) is a rare condition characterized by painful indurated cutaneous plaques infiltrated with mature neutrophils and may be accompanied by fever, granulocytosis, arthritis, and conjunctivitis. It is associated with various malignant and preneoplastic states, the most common being leukemia and myeloproliferative disorders. Its association with solid tumors is infrequent. The case described here represents, to our knowledge, the first report of Sweet syndrome in a patient with osteogenic sarcoma, a primary tumor of bone arising from mesenchymal cells.

Adult↗
PubMed1996

Etoposide achieves potentially cytotoxic concentrations in CSF of children with acute lymphoblastic leukemia.

PURPOSE: Although epipodophyllotoxins are commonly used in contemporary treatment regimens for acute lymphoblastic leukemia (ALL), their potential role in CNS-directed therapy has received little attention. We prospectively studied 20 children during initial remission of ALL and 16 children at relapse to assess CSF penetration of etoposide. METHODS: Simultaneous plasma and CSF concentrations were assessed at a median of 2.8 hours (range, 0.4 to 5.3) after an intravenous (i.v.) or oral dose in 41 paired samples. RESULTS: Etoposide given at 300 mg/m2 i.v. to patients during first remission and at 50 or 25 mg/m2 orally to those in relapse resulted in median CSF levels of 0.175 mumol/L (range, .066 to 2.12), 0.011 mumol/L (range, .004 to .032), and 0.007 mumol/L (range, .003 to .014), respectively. The CSF etoposide concentration was > or = 10 nmol/L in 20 of 20, five of 10, and two of 11 courses following 300 mg/m2 i.v., 50 mg/m2 orally, and 25 mg/m2 orally, respectively, and was positively related to both the concurrent etoposide plasma concentration (R2 = .64) and to dose (R2 = .73). The median ratio of CSF to plasma concentration was 0.30% (range, 0.09% to 3.12%), which was not related to dose, plasma concentration, or time postdose at which samples were obtained, but was positively correlated with the CSF protein concentration (R2 = 0.43, P = .006). Both the absolute etoposide CSF concentrations (P = .008) and the ratio of CSF to plasma concentrations (P = .023) were higher among first-remission patients who had CSF leukemic blasts at diagnosis compared with those without CSF blasts. CONCLUSION: Because etoposide concentrations as low as 10 nmol/L may be cytotoxic in vitro, prolonged daily oral low-dose (50 mg/m2) or conventional i.v. doses of etoposide may contribute to successful CNS-directed therapy in children with ALL.

Administration, Oral↗
PubMed1996

Allopurinol inhibits de novo purine synthesis in lymphoblasts of children with acute lymphoblastic leukemia.

Allopurinol is used to prevent hyperuricemia in newly diagnosed patients with acute lymphoblastic leukemia (ALL). Although allopurinol has been shown to inhibit de novo purine synthesis (DNPS) in fibroblasts in vitro, this effect has not been assessed in ALL lymphoblasts. We assessed DNPS in ALL lymphoblasts in 46 consecutive patients with ALL. DNPS was determined by 14C-formate incorporation in purine bases both at diagnosis (n = 46) and 44h after MTX therapy +/- allopurinol (n = 31). The 27 patients who had received no allopurinol prior to the diagnostic bone marrow aspirate had significantly higher rates of DNPS (median, 102 fmol new purines/nmol total purines/h) compared to the 12 patients who had received more than one dose of allopurinol (100 mg/m2 orally) (median, 2.3 fmol/nmol/h; P < 0.001); the seven patients who received one dose of allopurinol had intermediate rates of DNPS (median, 58.5 fmol/nmol/h). Among patients who were evaluable for MTX effects at 44h (n = 31), the percent inhibition of DNPS was greater in the eight patients who received concomitant allopurinol (median, 100% inhibition) compared to the 23 patients who received only methotrexate therapy (median, 89% inhibition, P = 0.03). These data indicate that allopurinol suppresses may contribute to the decrease in circulating blasts in patients with newly diagnosed acute leukemias.

Adolescent↗
PubMed1996

Prognostic factors in the acute lymphoid and myeloid leukemias of infants.

The age boundaries and prognostic factors that define the infant leukemias are still controversial. We therefore analyzed event-free survival according to age group in 96 children treated for acute lymphoblastic leukemia (ALL) and 51 treated for acute myeloid leukemia (AML) before the age of 2 years. The study population was registered in consecutive institutional trials of multiagent chemotherapy conducted between 1980 and 1994. Among infants with ALL, event-free survival was significantly poorer in the 0- to 6-month-old group than in patients treated between 6 and 12 months of age (P = 0.03), whose outcome was in turn inferior to that in the 12- to 18-month and 18- to 24-month age groups (P = 0.013). Leukemic cells from ALL patients younger than 12 months had a significantly higher frequency of 11q23/MLL abnormalities, as well as better growth in stromal cell culture, compared to lymphoblasts from the older groups (P < 0.01). The only independent predictor of adverse prognosis among infants diagnosed with ALL before age 12 months was the presence of an 11q23/MLL rearrangement (P = 0.03). These findings contrast sharply with results for the AML cohort, whose event-free survival did not vary significantly by age group (P = 0.58). Male sex (P = 0.01) and leukocyte count > or = 50 x 10(9/l) (P = 0.04), but not 11q23 abnormalities, were independently associated with a poorer outcome for children with AML younger than 12 months at diagnosis. Thus, in very young children with ALL (but not AML), the rearrangement status of the 11q23/MLL region supersedes age group as a determinant of treatment outcome.

Age Factors↗
PubMed1995

Persistence of circulating blasts after 1 week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia.

Early response to therapy, typically assessed by bone marrow status, is predictive of outcome in childhood acute lymphoblastic leukemia (ALL). Less is known about the significance of early clearance of blast cells in peripheral blood. We reviewed medical records of all patients with ALL enrolled on St Jude Total Therapy Study XI (February 1984 to September 1988) to determine the presence of blast cells in peripheral blood at diagnosis and after 1 week of intensive induction therapy. Of the 358 patients, 59 lacked evidence of circulating blast cells at diagnosis, and data were unavailable for 2 patients. The prognostic significance of persistent circulating blast cells in the remaining 297 patients was assessed in a multivariate analysis that included known adverse prognostic factors. Persistent circulating leukemic blasts were present at day 8 in 41 patients (14%). Compared with the "blast-negative" group, these patients had a significantly higher frequency of several adverse clinical features (leukocyte count > 50 x 10(9)/L, mediastinal mass, central nervous system leukemia, T-cell phenotype, lack of CD10 expression, and L2 morphology) and a significantly poorer 5-year event-free survival (34% +/- 8% [SE] v 77% +/- 3%, P < .01). By multivariate analysis, blast cell persistence at week 1 was the most significant adverse feature in the overall cohort (relative risk, 2.9; 95% confidence interval, 1.8 to 4.8) and in an analysis limited to B-lineage cases (relative risk, 3.6; 95% confidence interval, 1.9 to 7.1). Patients identified by this simple, noninvasive measure may benefit from early modification of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Molecular detection of the (2;5) translocation of non-Hodgkin's lymphoma by reverse transcriptase-polymerase chain reaction.

The t(2;5)(p23;q35) translocation was initially identified in cases of anaplastic large-cell lymphoma (ALCL) that expressed the Ki-1 (CD30) antigen. We have recently cloned this translocation and shown it to encode a chimeric product consisting of the N-terminal portion of a nonribosomal nucleolar phosphoprotein, nucleophosmin (NPM), from chromosome 5, fused to the kinase domain of a novel transmembrane tyrosine-specific protein kinase, anaplastic lymphoma kinase (ALK), from chromosome 2. To better define the spectrum of lymphomas that contain this translocation, we have analyzed 70 cases of non-Hodgkin's lymphoma (NHL) for expression of the t(2;5)-derived NPM/ALK chimeric message by reverse transcriptase-polymerase chain reaction (RT-PCR). Using a previously described set of oligonucleotide primers, NPM/ALK chimeric transcripts were detected in 21 of 22 cases that contained the t(2;5) by cytogenetic analysis and in 10 of 48 cases that either lacked evidence of the t(2;5) or had unsuccessful cytogenetics. In all but 1 case, the NPM/ALK PCR products were of identical size and sequence, suggesting that the genomic chromosome breaks are clustered in a single intron in both NPM and ALK. The NPM/ALK-expressing cases were not confined to NHLs with anaplastic morphology and included 15 ALCLs, 6 immunoblastic lymphomas, and 10 diffuse large-cell lymphomas. Moreover, only slightly greater than half of the cases with anaplastic morphology and 59% of CD30-expressing cases were NPM/ALK positive. Thus, neither anaplastic morphology nor the expression of CD30 accurately predicted the presence of this molecular genetic subtype of lymphoma.

Adult↗
PubMed1995

Childhood lymphoma: diagnostic accuracy of chest radiography for severe pulmonary complications.

INTRODUCTION: We sought to determine whether chest radiography can be reliably used to distinguish persistent or relapsing pulmonary lymphoma from a variety of infectious and noninfectious pulmonary conditions that can occur in children receiving treatment for lymphoma. METHODS: We studied chest radiographs of 37 patients (30 with non-Hodgkin's lymphoma, and seven with Hodgkin's disease) who died of paediatric lymphoma or of treatment complications. Pulmonary findings at autopsy comprised lung tumour (n = 14), pleural tumour (n = 12), pneumonia (n = 22), adult respiratory distress syndrome (ARDS; n = 16), haemorrhage (n = 27), and infarction (n = 13). Using a 4-point scale and without knowledge of autopsy findings, three radiologists independently rated antemortem radiographs for the presence of pulmonary tumour, pleural tumour, pneumonia in general, pneumonia caused by viral, bacterial, fungal, and protozoan pathogens, ARDS, pulmonary haemorrhage, and pulmonary infarction. Diagnostic accuracy was defined by the area under the receiver-operating-characteristic curve (AZ). RESULTS: Diagnostic accuracy was good for pulmonary tumour (AZ, 0.71 +/- 0.6), protozoan pneumonia (AZ, 0.77 +/- 0.06), and ARDS (AZ, 0.86 +/- 0.07) but poor for all other conditions. The absence of both pleural effusions and mediastinal/right hilar lymphadenopathy was significantly associated (P < or = 0.04) with the absence of lung tumour. DISCUSSION: The pulmonary processes in these patients can all demonstrate diffuse airspace opacification, and many patients had multiple lung abnormalities at autopsy. The radiologist-readers were unable to identify which pulmonary conditions were responsible for radiographic findings in most patients. The readers were able to identify patients who did not have pulmonary lymphoma. If pulmonary involvement with lymphoma is unlikely, bronchoscopy with bronchoalveolar lavage may be sufficient to establish a diagnosis. When pulmonary lymphoma is a clinical consideration, open lung biopsy is usually required for diagnosis.

Adolescent↗
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↗
PubMed1995

L-asparaginase may potentiate the leukemogenic effect of the epipodophyllotoxins.

The risk for induction of epipodophyllotoxin-related acute myeloid leukemia (AML) depends largely on the schedule of drug administration and, to a lesser degree, the cumulative dose. Concomitant use of other genotoxic drugs, such as alkylating agents and cisplatin, can increase the hazard further. We have treated 154 consecutive higher-risk cases of acute lymphoblastic leukemia in our recent Total Therapy Study XIII with an intensive post-remission regimen of chemotherapy that included etoposide given every other week or less often-a schedule associated with a relatively low cumulative incidence of secondary AML in our Study XI. Unexpectedly, four patients have developed secondary AML at 12 to 23 months from the start of treatment (median, 16 months). The 2-year cumulative risk estimate significantly exceeds that for 185 historical controls in Study XI whose continuation regimen included epipodophyllotoxins every other week: 5.4% (95% confidence interval, 0-11%) compared with 1.1% (0-2.6%), P = 0.046. Compared to patients treated in Study XI, those enrolled in Study XIII receive fewer scheduled doses of epipodophyllotoxin (48 (all etoposide) vs 63 (30 etoposide, 33 teniposide)) but 16 to 19 additional doses of L-asparaginase and eight additional doses of high-dose methotrexate, all within the week preceding etoposide treatment. We attribute the apparently increased rate of secondary AML in Study XIII to the use of L-asparaginase immediately before etoposide administration. On this schedule, the enzyme could increase systemic exposure to etoposide or its catechol metabolites and reduce the ability of cells to repair DNA damage.

Acute Disease↗
PubMed1995

Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases.

To define better the risk of epipodophyllotoxin-related acute myeloid leukemia (AML) after extended follow-up and to assess responses to intensive salvage therapy, all patients who developed this complication after treatment for acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) in consecutive clinical trials at St Jude Children's Research Hospital from 1979 to 1994 were studied. Cases with 'lineage switch' or 'clonal selection' were excluded. Epipodophyllotoxin-related AML developed in 32 of 1140 patients treated for ALL and in three of 332 treated for NHL; it was a first adverse event in 25 and two cases, respectively. The complication was diagnosed at 12-130 months (median 34 months) after the initiation of treatment with epipodophyllotoxins; all but one of the cases occurred within 73 months, indicating that the risk is negligible after 6 years. The predominant karyotypic feature was 11q23 translocations (71% of cases); 21q22 rearrangements were rare. In a stepwise Cox regression analysis, two factors increased the risk of this complication: weekly or twice weekly administration of epipodophyllotoxins (P < 0.001); and the administration of asparaginase immediately before epipodophyllotoxin therapy (P < 0.001). Initial responses to salvage therapy were comparable to those reported for de novo AML: 92% of the evaluable patients entered complete remission after combination treatment. Single-agent therapy with 2-chlorodeoxyadenosine induced complete or partial remissions in one-half of the patients treated. The long-term survival rate was dismal. Of the 17 evaluable patients treated exclusively with chemotherapy, only one is alive at 84 months, compared to three of 16 patients who underwent bone marrow transplantation (alive at 10, 23 and 73 months). Cases of epipodophyllotoxin-related AML constitute a unique clinical syndrome that will require innovative strategies for cure.

Acute Disease↗
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

Intensive chemotherapy for Philadelphia-chromosome-positive acute lymphoblastic leukaemia.

Childhood acute lymphoblastic leukaemia with the classic Philadelphia chromosome translocation is fatal in patients treated with chemotherapy alone. We report probable cures in three adolescents and one child who received extensively reinforced, early chemotherapy followed by rotational treatment with pairs of non-cross-resistant drugs. The median duration of leukaemia-free survival in this subgroup is 6.5 years (range 6-8 years). The two patients with long-term bone marrow surveillance for residual disease showed no evidence of the Philadelphia chromosome at 31 and 53 months post-remission. Such intensive chemotherapy is a reasonable option for patients who are not able to undergo bone marrow transplantation.

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

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

Immunologic, cytogenetic, and clinical characterization of childhood acute lymphoblastic leukemia with the t(1;19) (q23; p13) or its derivative.

PURPOSE: To evaluate the immunophenotypes, karyotypes, and clinical features, including treatment responses, of patients with childhood acute lymphoblastic leukemia (ALL) and either a t(1;19)(q23;p13) or a der(19)t(1;19)(q23;p13) translocation. PATIENTS AND METHODS: The lymphoblasts of 45 patients with a balanced translocation, t(1;19) or its derivative form, der(19)t(1;19), were analyzed by cytogenetic and immunologic methods for differences that might suggest distinct subtypes of ALL. This cohort was treated in four consecutive clinical trials with a median overall follow-up duration of 7 years. RESULTS: A pre-B immunophenotype was found in 10 cases with the balanced t(1;19) and 31 with the unbalanced der(19)t(1;19). The four remaining cases, each with a derivative t(1;19), were classified as early pre-B ALL. The characteristic surface antigen profile of the 41 pre-B cases was CD19+/CD10+/CD22+/CD34-/CD20+/-, whether the translocation was balanced or derivative. In contrast to the four early pre-B cases, which had hyperdiploid karyotypes (> 50 chromosomes), the pre-B cases were primarily pseudodiploid. Comparison of presenting clinical and laboratory features, as well as event-free survival, failed to disclose any differences that would warrant separation of pre-B cases with a balanced or derivative translocation. However, neither subgroup responded to therapy as well as patients with early pre-B ALL, each of whom remains in complete remission for > or = 3 years. CONCLUSION: The t(1;19) and the der(19)t(1;19) identify a relatively homogeneous group of patients with pre-B ALL, who can be expected to respond similarly to intensive chemotherapy. The exceptional cases have an early pre-B phenotype with hyperdiploid karyotypes and appear to have favorable prognosis.

Adolescent↗
PubMed1994

Phase I study of topotecan for pediatric patients with malignant solid tumors.

PURPOSE: To determine the dose-limiting toxicity and potential efficacy of topotecan in pediatric patients with refractory malignant solid tumors. PATIENTS AND METHODS: In this phase I clinical trial, 27 patients received topotecan 0.75-1.9 mg/m2 by continuous intravenous infusion daily for 3 days. Fifty-three treatment courses were given to these patients. RESULTS: Myelosuppression was the dose-limiting toxicity at levels of 1.3 to 1.9 mg/m2 for 3 days, requiring significant support with transfused packed RBCs and platelets. Myelosuppression was variable in severity at the 1.0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF). Other toxicities were not significant. One patient with neuroblastoma had a complete response that lasted for 8 months. Stable disease activity was recorded for other patients with neuroblastoma, rhabdomyosarcoma, and islet cell carcinoma. Pharmacokinetic studies showed that topotecan plasma concentrations ranged from 1.6 to 7.5 ng/mL during infusions of 1.0 mg/m2/d, and that there was a biphasic plasma distribution with a mean terminal half-life of 2.9 +2- 1.0 hours. CONCLUSION: Topotecan is a promising anticancer agent that deserves phase II testing in pediatric solid tumors. We recommend that pediatric phase II topotecan trials use 1.0 mg/m2/d for 3 days as a constant intravenous infusion, followed by G-CSF for 14 days, and that these treatment courses be repeated every 21 days.

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↗