Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate ('Orange') in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a children's cancer group report.

Despite prolonged therapy (18 months), children with advanced non-lymphoblastic, non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG) trials achieved less than a 60% 5-year event-free survival (EFS). In this study we piloted a shorter but more intensive protocol ('Orange') to determine the feasibility, safety, and efficacy of this alternative treatment approach. Thirty-nine children received a CHOP-based induction, etoposide/ifosfamide consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside (Ara-C) and L-asparaginase) intensification, and either one or two similar but less intense maintenance courses. Patients were stratified to standard-risk (5 months) vs high-risk (7 months) treatment. High risk was defined as either bone marrow disease, CNS disease, mediastinal mass > or = one-third thoracic diameter at T5 and/or LDH > or =2 times institutional upper limits of normal. All other patients were considered to be standard risk. Results were compared with the previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered standard- vs. high-risk, respectively. The 5-year EFS and overall survival (OS) were 77 +/- 7% and 80 +/- 7%, respectively. The 5-year EFS and OS were significantly better in the standard- vs. high-risk subgroups (100% vs. 61 +/- 11%) (P < 0.003) and (100% vs. 65 +/- 11%) (P < 0.01), respectively. Lactate dehydrogenase (LDH) > or =2 x normal (NL) was associated with significantly poorer outcomes (LDH > or =2 x NL vs. <2 x NL) (5-year EFS: 55 +/- 12% vs. 100%) (P < 0.0004). This CCG hybrid regimen, 'Orange', of short and more intensive therapy resulted in a significant improvement in outcomes compared with the previous CCG trial of more prolonged but less intense therapy. This regimen that deletes high-dose methotrexate, if confirmed in a larger trial, could be considered as an alternative treatment approach in children without high tumor burdens (LDH <2 x NL) and Murphy stage III disease.

Comparison of long-term outcome of children and adolescents with disseminated non-lymphoblastic non-Hodgkin lymphoma treated with COMP or daunomycin-COMP: A report from the Children's Cancer Group.

BACKGROUND: Early Children's Cancer Group (CCG) trials indicated that the cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) regimen was superior to the LSA2L2 regimen for non-lymphoblastic (NLB) non-Hodgkin lymphoma (NHL). Studies by other groups suggested that addition of anthracyclines to standard therapies could improve outcome. Therefore, in 1983 CCG initiated study CCG-503, a randomized trial of COMP vs. daunomycin-COMP (D-COMP) in children and adolescents with disseminated NLB NHL. PROCEDURES: Between December 1983 and April 1990, 404 eligible patients were entered. Patients without central nervous system (CNS) or marrow involvement were randomized to receive COMP (N = 139) or D-COMP (N = 145). Randomization was stratified by histology and site of disease. Patients with CNS or marrow involvement (stage IV) were non-randomly treated with D-COMP (N = 120). RESULTS: Ten-year event-free survival in COMP and D-COMP patients was similar: 55 +/- 4.3% (Estimate +/- SE) vs. 57 +/- 4.2% (not significant). Stage I-III patients with large-cell (LC) NHL had worse 10-year event-free survival (EFS) (48 +/- 4.9%) than those with small non-cleaved cell (SNCC) NHL disease (61 +/- 3.5%, P < 0.05 in multivariate analysis), but equivalent survival (65 +/- 4.7% vs. 63 +/- 3.5%) due to significantly higher salvage rates in LC patients, especially those failing more than 12 months from diagnosis. Ten-year EFS in stage IV patients was 39 +/- 5.2%. Addition of daunomycin resulted in higher rates of grade 3/4 hematologic toxicity and stomatitis, as well as late cardiac-related deaths. The incidence of second malignant neoplasms was 1.0% at 10 years. CONCLUSIONS: Addition of daunomycin to standard COMP therapy did not improve outcome in pediatric disseminated NLB NHL. Patients with LC disease had a significantly reduced long-term EFS, but were retrieved at a higher rate than patients with SNCC disease, resulting in equivalent long-term survival.

Chemoreduction for retinoblastoma may prevent intracranial neuroblastic malignancy (trilateral retinoblastoma).

OBJECTIVE: To evaluate whether neoadjuvant intravenous chemotherapy (chemoreduction) for retinoblastoma reduces the risk for associated intracranial neuroblastic tumor (trilateral retinoblastoma). DESIGN: Retrospective consecutive case series. PARTICIPANTS: Two hundred fourteen consecutive children with newly diagnosed retinoblastoma treated at a major ocular oncology center from January 1, 1995, to July 1, 1999. MAIN OUTCOME MEASURE: Development of associated intracranial neuroblastic tumor (trilateral retinoblastoma). RESULTS: During the 54-month study period, 142 patients (66%) received chemoreduction (consisting of vincristine sulfate, etoposide phosphate, and carboplatin therapy) as part of their treatment strategy (chemoreduction group), whereas 72 (34%) were treated with nonchemoreduction methods (nonchemoreduction group). In the chemoreduction group, no associated intracranial neuroblastic tumor developed during the mean 47-month follow-up. Based on a recent meta-analysis of the prevalence of trilateral retinoblastoma, we would have expected the intracranial tumor to develop in 5 to 15 patients with hereditary retinoblastoma. This lack of associated trilateral retinoblastoma in the chemoreduction group was significantly less than expected using binomial distribution (P<.001). In the nonchemoreduction group, associated intracranial tumor (pinealoblastoma) developed in 1 patient, a finding consistent with the expected frequency. CONCLUSION: Chemoreduction protects against the highly fatal associated intracranial neuroblastic tumor (trilateral retinoblastoma). This observation is especially important in children with bilateral or familial retinoblastoma who are at greatest risk for this brain tumor.

Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912.

PURPOSE: To determine the toxicity and response rate in children treated with dexamethasone, etoposide, cisplatin, high-dose cytarabine, and L-asparaginase (DECAL) for recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow transplantation or up to four cycles of ifosfamide, mesna, and etoposide alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL induction therapy, complete response (CR) or partial response (PR) was reported in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58 patients with NHL who were assessable for response were considered, the response rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively. Five-year event-free survival was 26% +/- 9% and 23% +/- 5% in patients with HD and NHL, respectively. Five-year survival was 31% +/- 14% and 30% +/- 6%, respectively. Although median time to treatment failure was significantly longer in patients with HD (EFS, P =.002; survival, P =.011), this difference did not translate into a higher long-term survival. Grade 3 or 4 toxic effects were observed during induction in 70 (72%) of 97 patients and during maintenance in 45 (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in particular were frequently observed. Other toxic effects were uncommon. Although not a formal part of the therapy or the study design, 42 patients who responded to therapy who underwent bone marrow transplant did not show any benefit from this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.

Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.

BACKGROUND: Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS: METHODS: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided. RESULTS: In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up. CONCLUSIONS: Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.

Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease.

PURPOSE: The outlook for children and adolescents with Hodgkin disease (HD) is excellent with combined modality therapy. However, the long-term toxicities of multiagent therapy and radiation therapy remain of concern for these patients with curable disease. In an attempt to reduce long-term toxicities while preserving excellent cure rates, we developed a combined-modality protocol using a modified seven-drug hybrid and low-dose (2,000 cGy) involved field radiation therapy (RT). The hybrid used cumulative doses of alkylating agents and anthracyclines that were lower than those used in previous four-drug regimens and substituted a less leukemogenic agent, cyclophosphamide, for nitrogen mustard. PATIENTS AND METHODS: From 1991 through 1994 a cyclophosphamide, vincristine, procarbazine, and prednisone/adriamycin, bleomycin, and vinblastine hybrid was used to treat 29 patients with HD. Median age was 12 years (range 6-16 yrs). Patients who were postpubertal with early stage disease as determined by surgical staging were excluded. Treatment consisted of four cycles of therapy for stages I and IIA, six cycles for stages IIB and III, and eight cycles for stage IV. Twenty-two patients also received low-dose RT to areas of bulky disease. RESULTS: Twenty-eight patients (97%) had a complete response to chemotherapy. Five patients experienced relapse; two died from disease 27 and 29 months after initial diagnosis; three received additional therapy and are alive with no evidence of disease. Follow-up for all other patients is a median of 56 months (range 24-78 mos) from cessation of therapy and all have remained disease-free. At 5 years follow-up, actuarial disease-free survival is 82%, and the overall survival is 93%. There have been no clinically significant cardiac or pulmonary toxicities and no secondary malignancies. CONCLUSIONS: This therapy has resulted in 5-year overall survival and disease-free survival rates similar to regimens using higher doses of alkylating agents, anthracyclines, and radiation. Longer follow-up will be necessary to fully evaluate disease-free survival, organ damage, and quality of life.

Vitrectomy in eyes with unsuspected retinoblastoma.

OBJECTIVE: To analyze patient management and prognosis after vitrectomy in eyes with unsuspected retinoblastoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Eleven consecutive patients who had undergone vitrectomy on an eye with unsuspected retinoblastoma. MAIN OUTCOME MEASURES: The two main outcome measures were ultimate patient management and the development of retinoblastoma metastasis. RESULTS: Of more than 900 consecutive patients with retinoblastoma managed on the Ocular Oncology Service at Wills Eye Hospital in Philadelphia, 11 (1%) had prior vitrectomy in an eye with viable tumor before referral to us for suspected retinoblastoma. The main preoperative diagnoses included vitreous hemorrhage in seven patients (64%), toxocariasis in two patients (18%), toxoplasmosis in one patient (9%), and endophthalmitis in one patient (9%). In no case was retinoblastoma suspected before vitrectomy. The mean patient age at vitrectomy was 6 years. Retinoblastoma was later suspected during vitrectomy in two patients (18%), on cytologic examination of the vitrectomy specimen in eight patients (73%), and after referral in one patient (9%). The mean interval between vitrectomy and referral to us was 23 days. On examination, the globe was classified as Reese-Ellsworth group Vb in all 11 patients (100%). Anterior chamber tumor cells were clinically visible in four eyes (36%), hyphema in two eyes (18%), and iris neovascularization in two eyes (18%). Retinoblastoma cells were visualized in the vitreous in seven eyes (64%) and not visualized in four eyes (36%) that had vitreous blood. Enucleation was necessary in all 11 patients (100%). Adjuvant treatment was delivered in 10 patients (91%), using orbital radiotherapy in nine patients (82%) and chemotherapy in nine patients (82%). Histopathologic evidence of retinoblastoma invasion was documented in the episclera (two eyes; 18%), anterior chamber (seven eyes; 64%), iris (five eyes; 45%), ciliary body (five eyes; 45%), choroid (three eyes; 27%), and optic nerve (four eyes; 36%; prelaminar, two eyes; postlaminar, two eyes). The vitrectomy ports, Tenon's fascia, cut end of the optic nerve, and orbit were free of tumor. Of the 10 patients who received prophylactic chemotherapy, radiotherapy, or both in addition to enucleation for prevention of retinoblastoma metastasis, none (0%) experienced metastasis or orbital recurrence during the mean follow-up of 7 years (range, 0.2-24 years) from the time of retinoblastoma diagnosis. However, one patient was referred to us after the development of metastatic retinoblastoma, and despite aggressive chemotherapy and radiotherapy after enucleation, died 24 months later. CONCLUSIONS: Retinoblastoma may present with atypical features such as vitreous hemorrhage or signs of vitreous inflammation, particularly in older children. Vitrectomy should be avoided in these cases until the possibility of underlying retinoblastoma is excluded. If vitrectomy is performed in an eye with unsuspected retinoblastoma, enucleation combined with adjuvant chemotherapy, radiotherapy, or both without delay is advised to prevent systemic tumor dissemination.

Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: role of cranial irradiation.

BACKGROUND: The risk factors responsible for an increased prevalence of obesity or overweight in survivors of acute lymphoblastic leukemia (ALL) remain controversial. We evaluated changes in body mass index (BMI) in a cohort of ALL survivors, all of whom have been followed until completion of linear growth. PROCEDURE: BMI (weight/height(2)) was used as an index of adiposity and was calculated at diagnosis, at the end of treatment, and at attainment of final height in a cohort of 126 (59 males) survivors of ALL. BMI was adjusted for age and sex by computing a BMI standard deviation score (SDS) or z score. The spectrum of therapies used included intrathecal chemotherapy given alone (n = 38) or combined with cranial irradiation (CRT; 18 Gy, n = 35; 24 Gy, n = 53) and exposure to prednisone at a low dose (<3.5 gm, n = 49), medium dose (3.5-9.4 gm, n = 46), or high dose (>9.4 gm, n = 30). RESULTS: Overall, mean +/- SEM BMI-SDS increased significantly between diagnosis (-0.18 +/- 0.08) and the end of therapy (0.41 +/- 0.09, P < 0.01), with no significant change thereafter. For patients without CRT, mean BMI-SDS remained unchanged, whereas, for those so treated, mean BMI-SDS increased significantly between diagnosis and the completion of therapy (P < 0.001). The change in mean BMI-SDS was greater in the 24 Gy group vs. the 18 Gy CRT sample (P < 0.005). In a multivariate logistic regression model, CRT was an independent predictor of being overweight (BMI >/=85 percentile) at attainment of final height [odds ratio = 1.6 (95% confidence interval 1.0-23. 1)]. The percentage of subjects who were overweight at attainment of final height was 10.5%, 40%, and 38% for subjects treated with no CRT, 18 Gy CRT, or 24 Gy CRT, respectively (P < 0.01). CONCLUSIONS: Children with ALL given CRT develop increases in their BMI-SDS early on and during treatment and remain at significant risk for becoming overweight as young adults, a development that may increase their already heightened risk for various adverse health outcomes.

Long term survivors of childhood leukemia.

Changes in therapy, primarily intensification, for childhood leukemias have significantly improved cure rates during the past 30 years. The increasing number of survivors has led to a heightened appreciation of the late complications of treatment caused by both radiation and chemotherapy. Important late effects include decreased growth, poor school performance, altered cardiac function, infertility, and second malignant neoplasms. The long term outcome of children and adolescents suffering from the most recently recognized acute complication of treatment, avascular necrosis of weight-bearing bones, is still not known. These, and all patients treated on clinical trials, should be followed throughout their lives. Many of the complications of treatment are often not realized until years after the completion of therapy; some have been found to be related to dose intensity, emphasizing the importance of clinical trials that examine reduction of therapy for diseases with excellent cure rates. A successful example of this strategy is the elimination or reduction of radiation dose for the prevention of central nervous system acute lymphocytic leukemia. This has resulted in fewer long term central nervous system complications without a decrease in survival rates. As knowledge of late effects increases, design of future trials will need to focus on striking a balance between cure and long term toxicity.

Outcome of CNS disease at diagnosis in disseminated small noncleaved-cell lymphoma and B-cell leukemia: a Children's Cancer Group study.

PURPOSE: To examine the impact of initial CNS involvement on outcome and patterns of failure in patients with disseminated small noncleaved-cell lymphoma and B-cell leukemia who were treated in four successive Children's Cancer Group trials. PATIENTS AND METHODS: Of 462 patients with disseminated disease, 49 (10.6%) had CNS disease at diagnosis (CNS+). CNS disease included meningeal disease or CNS parenchymal masses with or without cranial neuropathies (CSF+/Mass; CNPs) in 36 patients and isolated CNPs in 13. Of the CNS+ patients, 28 had M2 (5% to 25% blasts) or M3 (> 25% blasts) bone marrow involvement. All patients received protocol-based systemic and intrathecal chemotherapy. Thirty-six patients also received CNS irradiation. RESULTS: Relapses occurred in 21 (43%) of 49 patients, predominantly in the CNS (71%) and bone marrow (52%). The 3-year event-free survival +/- SE for all patients with CNS+ disease was 45% +/- 7%. Patients with CSF+/Mass had a nominally higher treatment failure rate compared with patients with CNS- after adjusting for marrow status and lactate dehydrogenase (LDH) diagnosis, with a relative failure rate (RFR) of 1.52 (95% confidence interval [CI], 0.88 to 2.6; P =.15). In comparison, the RFRs for patients with M2 or M3 marrow and for those with LDH levels greater than 500 IU/L after adjusting for CNS disease were 1.4 (95% CI, 0.96 to 2.0; P =.029) and 2.2 (95% CI, 1.5 to 3.0; P <.001), respectively. The RFR for patients with isolated CNPs was 0.87 (95% CI, 0.36 to 2.1; P =.76). CONCLUSION: We conclude that, with the treatments used during the period covered by these studies, the presence of CSF+/Mass CNS disease at diagnosis was associated with a nominally worse outcome independent of initial bone marrow status and LDH level, but the effect was not statistically significant.

Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma.

PURPOSE: To study the effectiveness of combined systemic chemotherapy and local ophthalmic therapy for retinoblastoma with the goal of avoiding enucleation and external-beam radiation therapy (EBRT). PATIENTS AND METHODS: This was a prospective, nonrandomized, single-arm clinical trial. Seventy-five eyes were followed in 47 children. Patients were treated with a six-cycle protocol of vincristine, etoposide, and carboplatin. Most (83%) also received ophthalmic treatment (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy) during and/or after the chemotherapy. RESULTS: With a median follow-up of 13 months, event-free survival was 74%, with an event defined as enucleation and/or EBRT. Six children required EBRT in seven eyes (9%); five required enucleation of one eye (7%); five required a combination of EBRT and enucleation in six eyes (8%). Reese-Ellsworth groups 1, 2, and 3 eyes had excellent results, with avoidance of EBRT or enucleation in all 39. Treatment of groups 4 and 5 was less successful, with 33% of six eyes and 53% of 30 eyes, respectively, requiring EBRT and/or enucleation. Toxicities from chemotherapy were mild and included cytopenias (89%), fever and neutropenia (28%), infection (9%), and gastrointestinal symptoms, dehydration, and vincristine neurotoxicity (40%). No patients developed a second malignancy, metastatic disease, renal disease, or ototoxicity. CONCLUSION: In retinoblastoma patients with Reese-Ellsworth eye groups 1, 2, or 3, systemic chemotherapy used with local ophthalmic therapies can eliminate the need for enucleation or EBRT without significant systemic toxicity. More effective therapy is required for Reese-Ellsworth eye groups 4 and 5.

The role of renal salvage procedures for bilateral Wilms tumor: a 15-year review.

PURPOSE: We reviewed our experience with renal salvage procedures in patients with bilateral Wilms tumor to determine the clinical outcome. MATERIALS AND METHODS: From 1982 to 1997, 23 children with bilateral Wilms tumor were treated with partial nephrectomy at our institution, including 7 who were also treated with brachytherapy. Medical history, use and response to chemotherapy and brachytherapy, operative records, renal function, pathological results, survival, and techniques for partial and repeat nephrectomy and brachytherapy were reviewed. RESULTS: We treated 8 boys and 15 girls, of whom 21 who presented with synchronous bilateral Wilms tumor underwent primary chemotherapy followed by secondary partial nephrectomy. A total of 44 partial nephrectomies were performed and brachytherapy was done in 7 patients. Ten children have normal renal function and no disease, 10 are dead and 2 have metastatic disease. Anaplasia was the most significant factor associated with an unfavorable outcome (p = 0.003). Of the patients who were cured 60% had a positive response to initial chemotherapy compared with only 25% who had an unfavorable outcome (p = 0.09). No significant differences were noted with respect to gender, age at presentation, highest local tumor stage at presentation or initial nephrectomy. No patient treated with brachytherapy had local recurrence. CONCLUSIONS: Preoperative chemotherapy followed by nephron sparing surgery is indicated in patients with bilateral Wilms tumor, while in those with diffuse anaplasia nephron sparing surgery is contraindicated. Brachytherapy should be considered for treating local disease involving chemoresistant tumors.

Pesticide exposures in children with non-Hodgkin lymphoma.

BACKGROUND: The association between pesticide exposure and non-Hodgkin lymphoma (NHL) in adults has been the subject of numerous case-control and cohort studies. However, to the authors' knowledge, data regarding pesticide exposures in children diagnosed with NHL have been lacking. METHODS: The Children's Cancer Group conducted a study comparing 268 children who developed NHL or leukemia with bulk disease with a group of matched, randomly selected regional population controls. The telephone interviews of both the case and control mothers included selected questions regarding occupational and home exposures to pesticides around the time of the index pregnancy and exposure of the child. RESULTS: A significant association was found between risk of NHL and increased frequency of reported pesticide use in the home (odds ratio [OR] = 7.3 for use most days; trend P = 0.05), professional exterminations within the home (OR = 3.0; P = 0.002), and postnatal exposure (OR = 2.4; P = 0.001). Elevated risks were found for T-cell and B-cell lymphomas; for lymphoblastic, large cell, and Burkitt morphologies; and in both young (age < 6 years) and older children. There was an increased risk of NHL with occupational exposure to pesticides (OR = 1.7) that was not significant overall, but that was significant for Burkitt lymphoma (OR = 9.6; P < 0.05). CONCLUSIONS: The results of the current study provide further evidence linking pesticide exposure to the risk of NHL, but the authors were unable to implicate any specific agent.

Late effects of chemotherapy compared to bone marrow transplantation in the treatment of pediatric acute myeloid leukemia and myelodysplasia.

BACKGROUND: As more pediatric patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) survive, comparison of the late effects of various therapies becomes increasingly important. This study of survivors of AML is the largest to date comparing the late effects of patients treated with chemotherapy (CT) with or without irradiation (RT) or CT followed by bone marrow transplantation (BMT). PROCEDURE: In a retrospective review of 228 patients with AML or MDS from 1970 to 1995, 62 survived and had follow-up data available more than 1 year following completion of therapy. Ten patients with Down syndrome were excluded. Twenty-six received CT and 26 underwent BMT. Weight and height Z scores, endocrine, ophthalmologic, renal, and cardiac function following CT +/- RT or BMT +/- total body irradiation (TBI) were compared at a mean follow-up of 7.4 and 5.6 years, respectively. RESULTS: Both groups experienced a decrement in height and increase in weight. The mean height Z score in the CT group fell from -0.29 to -0.72 (P = 0.02) and mean weight Z score rose from -0.06 at diagnosis (T0) to 0.51 at last follow-up (T2) (P = 0.02), a finding no longer significant when patients who received RT were excluded. The mean height Z score in the BMT group fell from -0.17 at TO to -0.65 at T2 (P = 0.02), while the mean weight rose from 0.29 at T0 to 0.84 at T2, (P = 0.07). Six of 9 BMT adolescent girls experienced ovarian failure versus 0 of 11 girls treated with CT (P = 0.002). Seven adolescent CT males and seven BMT males showed normal pubertal progression. Two BMT patients require thyroid hormone supplementation, and one receives growth hormone. Six BMT patients and one CT patient developed cataracts, all of whom received irradiation (P = 0.10). Serum creatinine level, hypertension, or left ventricular shortening fraction were not different in the two groups. One BMT patient has chronic graft versus host disease. CONCLUSIONS: Growth, renal, and cardiac functions were similar in the two groups. The need for estrogen supplementation was more frequent following BMT. Recommendations concerning therapy for AML should depend on the probability of cure.

The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma.

OBJECTIVE: To determine the outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. METHODS: Prospective analysis of 27 eyes in 22 patients with group V retinoblastoma treated with either 2- or 6-cycle chemoreduction and focal treatment methods (argon laser photocoagulation, transpupillary thermotherapy, cryotherapy, and plaque radiotherapy). The need for external beam irradiation and the eventual globe salvage rate were assessed. Median follow-up was 28 months. RESULTS: There were 16 eyes in the 2-cycle chemoreduction treatment group and 11 eyes in the 6-cycle chemoreduction treatment group. No significant difference was noted between the 2 groups with respect to baseline patient and eye findings. After chemoreduction treatment, external beam irradiation was necessary in 12 (75%) of 16 eyes in the 2-cycle chemoreduction treatment group and in 4 (36%) of 11 eyes in the 6-cycle chemoreduction treatment group. There was no statistical difference between the 2- and 6-cycle chemoreduction treatment groups with respect to necessity for external beam irradiation (logistic regression analysis). All 4 eyes in the 2-cycle chemoreduction treatment group and 3 of 12 eyes in the 2-cycle chemoreduction treatment and irradiation group were eventually enucleated, the globe salvage rates being 0% and 75%, respectively. Two of 7 eyes in the 6-cycle chemoreduction treatment group and 1 of 4 eyes in the 6-cycle chemoreduction treatment and irradiation group were enucleated, the globe salvage rates being 71% and 75%, respectively. Except for the 2-cycle chemoreduction treatment group, in which the globe salvage rate was significantly lower (P = .03), there was no difference among the other 3 groups (2-cycle chemoreduction treatment and irradiation, 6-cycle chemoreduction treatment, and 6-cycle chemoreduction treatment and irradiation) with respect to globe salvage (logistic regression analysis). CONCLUSIONS: Local tumor control of group V retinoblastoma is possible with 6-cycle chemoreduction and focal therapy when external beam irradiation is not used. A larger sample size is necessary to determine how often external beam irradiation can be avoided.