Peter F. Coccia

Treatment of Anaplastic Histology Wilms' Tumor: Results From the Fifth National Wilms' Tumor Study

PURPOSEnAn objective of the fifth National Wilms Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms tumor (AH).nnnPATIENTS AND METHODSnProspective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation.nnnRESULTSnA total of 2,596 patients with Wilms tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively.nnnCONCLUSIONnThe prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.

B and T cell lymphomas: Analysis of blood and lymph nodes in 87 patients☆

B and T cell populations were studied in blood and neoplastic tissues from 64 untreated and 23 treated patients with non-Hodgkins lymphoma. This study was undertaken primarily to evaluate the relation of B and T cell markers in various lymphomas to the currently accepted morphologic classifications and to determine the utility of various tissues in defining the cell of origin of a lymphoma. When histologically involved blood, bone marrow, lymph nodes or body fluids were studied, a B or T cell origin of the lymphoma was identified in 26 of 28 (68 per cent) patients. A B cell origin was found in 17 adults classified as having nodular (N) or diffuse (D) poorly differentiated lymphocytic lymphoma (PDLL). One lymphoma of T cell origin was observed in an adult with poorly differentiated lymphocytic lymphoma-diffuse (PDLL-D). In contrast, all cases of PDLL-D in children were T cell in origin. The origin of American Burkitts (stem cell) lymphoma in two children was the B cell. When histologically involved blood was studied, a B or T cell origin was demonstrated in 10 of 21 (48 percent) adults. Evidence of a monoclonal proliferation of B lymphocytes in the blood was found two adults with more than 7 per cent lymphoma cells in Wright-Giemsa stained blood smears. When neoplastic lymph nodes were studied, the diagnosis of a B cell lymphoma was made in 8 of 12 (67 per cent) adults. Study of surface markers on malignant cells in cerebrospinal or serosal fluids frequently revealed a B or T cell origin of the lymphoma. B and T lymphocyte numbers in the blood did not correlate with immunoglobulin or skin test abnormalities. Abnormalities in circulating B or T cell percentages at diagnosis were a poor prognostic sign in patients with PDLL-D.

Autologous bone marrow transplantation for patients with relapsed hodgkin's disease

PURPOSEnHigh-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkins disease. Because patients with relapsed Hodgkins disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkins disease.nnnPATIENTS AND METHODSnWe treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT.nnnRESULTSnThe results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04).nnnCONCLUSIONnABMT is a more effective therapy when used early for patients with relapsed Hodgkins disease.

Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the national Wilms tumor study group

We evaluated the use of alternating cycles of cyclophosphamide/etoposide and carboplatin/etoposide in children entered on National Wilms Tumor Study (NWTS)‐5 who were diagnosed between August 1, 1995 and May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D, and doxorubicin (VAD) and radiation therapy (DD‐4A).

Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: A report from the National Wilms Tumor Study Group

NWTS‐5 was a multi‐institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed.

An increased frequency of 13q deletions detected by fluorescence in situ hybridization and its impact on survival in children and adolescents with Burkitt lymphoma: results from the Children’s Oncology Group study CCG-5961

Burkitt lymphoma (BL), an aggressive B‐cell malignancy, is often curable with short intensive treatment regiments. Nearly all BLs contain rearrangements of the MYC/8q24 region; however, recent cytogenetic studies suggest that certain secondary chromosomal aberrations in BL correlate with an adverse prognosis. In this multi‐centre study, the frequency and impact on clinical outcome of del(13q) and +7 in addition to MYC rearrangements as detected by fluorescence in situ hybridization (FISH) in children and adolescents with intermediate and high‐risk BL registered on Children’s Cancer Group study CCG‐5961 were investigated. Analysis with 13q14.3 and 13q34 loci specific probes demonstrated deletions of 13q in 38/90 (42%) cases. The loss of either 13q14.3 or 13q34 alone occurred in 14% and 8% respectively, while 20% exhibited loss of both regions. Gain of chromosome 7 was observed in 7/68 (10%) cases and MYC rearrangements were detected in 84/90 (93%). Prognostic analysis controlling for known risk factors demonstrated that patients exhibiting loss of 13q, particularly 13q14.3, had a significant decrease in 5‐year overall survival (77% vs. 95%, Pu2003=u20030·012). These observations indicate that del(13q) occurs in childhood BL at frequencies higher than previously detected by classical cytogenetics and underscores the importance of molecular cytogenetics in risk stratification.

Peripheral T-cell Lymphoma in Children and Adolescents: Role of Bone Marrow Transplantation

Although PTCL in children, as in adults, has a spectrum of clinical, morphologic, cytogenetic and immunologic features, there are several significant differences in these features between children and adults. Our data show that CD30 expression is much more common in pediatric PTCL than is reported in adult PTCL. Furthermore, the majority of children with CD30-positive PTCL do not have tumors with anaplastic large cell histology. Our data also suggest that the t(2;5) is not a specific marker of anaplastic large cell lymphoma in childhood. The likelihood of cure for children with PTCL is unclear, predominantly because of the lack of large numbers of pediatric patients with this less common entity. As with other NHL, we expect that treatment with conventional dose chemotherapy following relapse will be unsuccessful in most cases. Although the data are preliminary, it appears that high dose chemoradiotherapy followed by hematopoietic stem cell transplantation is an effective therapy in these patients. We have been particularly successful with a regimen based on thioTEPA, VP-16 and total body irradiation, but other regimens may also be efficacious. Further studies of this interesting group of tumors are clearly needed.

Increased risk of second malignant neoplasms in adolescents and young adults with cancer

The authors describe the incidence and characteristics of secondary malignant neoplasms (SMNs) in adolescent and young adult (AYA) cancer survivors compared with those in younger and older cancer survivors.

Acute lymphoblastic leukemia of NK-cell lineage: responses to IL-2.

Acute lymphoblastic leukemias with phenotypic characteristics of natural killer cell derived lineage are extremely uncommon. We identified an ALL with a phenotype consistent with an NK-cell of origin. The blasts underwent a proliferative response to r-IL2 in culture but showed no spontaneous or r-IL2 or gamma-INF induced cytotoxicity. With r-IL2 stimulation however, the tumor cells demonstrated a dramatic acquisition of low density CD8 surface positivity and a loss of CD11b expression after short term culture. By comparison to ALL of B or T lineage, NK ALL likely represents an early stage of bone marrow derived NK-cell precursor.

Early onset, EBV − PTLD in pediatric liver-small bowel transplantation recipients: a spectrum of plasma cell neoplasms with favorable prognosis

EBV(-) posttransplantation lymphoproliferative disorders (PTLDs) are rare compared with EBV(+) PTLDs, occur later after transplantation, and have a poor response to treatment. Few studies have reported EBV(-) PTLD in pediatric solid-organ transplantation recipients. We describe 5 cases of EBV(-) PTLD in recipients of combined liver and small bowel allografts ranging in age from 16 months to 7 years. EBV(-) PTLD developed 9-22 months (median, 15) after transplantation. Morphologically, the lesions ranged from atypical plasma cell hyperplasia (a term not currently included in the World Health Organization classification) to plasmacytoma like. In all cases, in situ hybridization for EBV was negative, and molecular studies demonstrated clonal IgH gene rearrangements. Protein electrophoresis showed multiple clonal paraproteins in 4 of 5 cases. In 2 cases with a donor-recipient sex mismatch, FISH cytogenetics demonstrated that the plasma cells were of mixed donor/recipient origin. One patient died before therapy. Four patients were treated with high-dose dexamethasone, and 1 patient subsequently required thalidomide. All 4 remain in remission 75-128 months (median, 86) after diagnosis. In contrast to reports of EBV(-) PTLD in adults, these plasma cell lesions occurred early after transplantation and resolved completely after minimal treatment.