"It's behaviors, not identity": Attitudes and beliefs related to HIV risk and pre-exposure prophylaxis among transgender women in the Southeastern United States.

HIV prevalence is high among transgender women (TGW) in the Southeastern U.S. Uptake of HIV Pre-Exposure Prophylaxis (PrEP) is low among TGW nationwide. We aimed to explore beliefs associated with PrEP among TGW in the Southeastern U.S., framed by the Health Belief Model. HIV-negative TGW ≥18 years old in Alabama participated in virtual focus group discussions. Authors coded and amended transcripts to explore emerging themes. Between July-December 2020, 17 TGW participated in 4 sessions. Mean age was 28.1±8.5 years. Several themes were identified: frustration with conflation of transgender identity and HIV risk, inappropriate transgender representation in PrEP advertising, concerns for interactions between PrEP and hormone therapy, perception that PrEP is meant for cisgender men who have sex with men and limited trans-affirming healthcare. Nuanced messaging is necessary to properly educate and engage TGW in HIV prevention strategies including PrEP given the diversity of this population.

CFTR function and clinical response to modulators parallel nasal epithelial organoid swelling.

In vitro biomarkers to assess cystic fibrosis transmembrane conductance regulator activity are desirable for precision modulator selection and as a tool for clinical trials. Here, we describe an organoid swelling assay derived from human nasal epithelia using commercially available reagents and equipment and an automated imaging process. Cells were collected in nasal brush biopsies, expanded in vitro, and cultured as spherical organoids or as monolayers. Organoids were used in a functional swelling assay with automated measurements and analysis, whereas monolayers were used for short-circuit current measurements to assess ion channel activity. Clinical data were collected from patients on modulators. Relationships between swelling data and short-circuit current, as well as between swelling data and clinical outcome measures, were assessed. The organoid assay measurements correlated with short-circuit current measurements for ion channel activity. The functional organoid assay distinguished individual responses as well as differences between groups. The organoid assay distinguished incremental drug responses to modulator monotherapy with ivacaftor and combination therapy with ivacaftor, tezacaftor, and elexacaftor. The swelling activity paralleled the clinical response. In conclusion, an in vitro biomarker derived from patients' cells can be used to predict responses to drugs and is likely to be useful as a preclinical tool to aid in the development of novel treatments and as a clinical trial outcome measure for a variety of applications, including gene therapy or editing.

Improved survival in primary nonmetastatic pediatric osteosarcoma of the extremity.

UNLABELLED: A prospective study using a dose-intensified neoadjuvant intra-arterial chemotherapy regimen was designed to improve survival rates of young patients with primary, nonmetastatic osteosarcoma of the extremity. Arteriography was implemented to individualize duration of therapy by serially assessing change in tumor neovascularity. Intravenous doxorubicin and intra-arterial cisplatin were administered repetitively at 3-week intervals until > or = 90% reduction in tumor neovascularity was achieved. Surgery was delayed until this good arteriographic response was documented. After resection, prediction of tumor neovascularity was compared with tumor necrosis. Since 1987, 62 eligible patients younger than 22 years old were treated with an average of four neoadjuvant courses. Toxicities were manageable. Fifty-four (87%) patients had a good histologic response. The rate of limb preservation surgery was 93.5% (58/62). Accuracy and sensitivity of serial arteriography in predicting histologic response were 92% and 98% respectively, and greatly assisted surgical planning. With an average followup of 91 months, estimated Kaplan-Meier survival at 10 years was 93% and event-free survival was 86%. Osteosarcoma survival rates were significantly improved by the use of this regimen compared with previously reported results. Serial arteriography succeeded in individualizing duration of neoadjuvant therapy and led to a higher rate of good histologic response. LEVEL OF EVIDENCE: Therapeutic study, level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

The Spanish National Institutes of Health-Chronic Prostatitis Symptom Index: translation and linguistic validation.

PURPOSE: The prominence of health related quality of life end points in international clinical research underscores the importance of well validated and translated measures to enable cross-cultural comparison. The National Institutes of Health (NIH)-Chronic Prostatitis Symptom Index (CPSI) assesses symptoms and health related quality of life in men with chronic nonbacterial, NIH type III prostatitis. To expand its use to Spanish speaking patients we performed a translation and linguistic validation. MATERIALS AND METHODS: The 9-item NIH-CPSI was translated into Spanish according to a standard methodology of 2 forward translations, 1 reconciled version, back translation of the reconciled version and 3 independent reviews by bilingual experts. The purpose of this methodology was to create a single universal Spanish version that would be acceptable to native Spanish speakers inside and outside of the United States. After the translation process the Spanish version was pre-tested in Argentina, Mexico, Spain and the United States. Patient responses were analyzed to identify necessary modifications. The internal consistency of the CPSI was evaluated using Cronbach's alpha. Pearson's product moment correlations were used to evaluate construct validity. RESULTS: Data were collected from chronic prostatitis patients, including 15 in Argentina, 15 in Mexico, 4 in the United States and 3 in Spain. The translation had high reliability overall and in all subscales (Cronbach's coefficient alpha = 0.81 to 0.94), and the subscales correlated well with each other (r = 0.76 to 0.97). However, patients expressed difficulty in distinguishing the response categories "a menudo" ("often") from "normalmente" ("usually") in question 3. We revised "a menudo" to "muchas veces" ("much of the time") and "normalmente" to "casi siempre" ("almost always") to improve the distinctiveness of response categories. CONCLUSIONS: The Spanish NIH-CPSI has high reliability as well as face and construct validity in Spanish speaking men from various countries. The Spanish NIH-CPSI permits cross-cultural comparisons of men with chronic nonbacterial prostatitis.

Long-term urological complications in survivors younger than 15 months of advanced stage abdominal neuroblastoma.

PURPOSE: We evaluated the long-term urological complications in survivors of infant advanced stage abdominal neuroblastoma. MATERIALS AND METHODS: The records of patients who presented during an 8-year period with surgical problems related to the kidney and who had survived advanced stage (IV and IV-S) neuroblastoma were reviewed. RESULTS: Of 7 patients identified 3 had complications of obstruction from retroperitoneal fibrosis and 4 had renal cell carcinoma. In the renal cell carcinoma group 3 patients had synchronous, multifocal, bilateral tumors and 1 had a tumor in a solitary kidney. Pathological examination of renal cell carcinoma revealed oncocytoidy with solid and papillary patterns. One patient underwent bilateral nephrectomy but in the remaining 3 renal preservation surgery was performed. All 7 patients have no progression of secondary complications 2 to 8 years after initial presentation. CONCLUSIONS: Survivors of advanced stage abdominal neuroblastoma may be predisposed to long-term urological complications well after initial diagnosis. Because of the risk of renal damage from obstruction secondary to retroperitoneal fibrosis, and the propensity to have renal cell carcinoma, close long-term followup using abdominal imaging is recommended.

Unusual childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4--anaplastic lymphoma kinase gene fusion.

This report describes an unusual extramedullary hematologic malignancy in an 18-month-old child who presented with a capillary leak syndrome that evolved into hyperleukocytosis with malignant cells. The circulating tumor cells did not express an antigen profile typical of any subtype of leukemia commonly observed in children. Tumor cells were CD3(-)/CD56(+); had germline TCR genes; and strongly expressed CD30, epithelial membrane antigen, and anaplastic lymphoma kinase (ALK) consistent with a null cell anaplastic large cell lymphoma (ALCL). The malignant cells contained a t(2;19)(p23;p13.1) that interrupted ALK and translocated it to the der(19). Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis revealed fusion of ALK to tropomyosin 4, an ALK fusion partner not described previously in hematologic malignancies. The clinical presentation and phenotypic features of this malignancy were not typical for ALCL because tumor cells expressed both myeloid (CD13, CD33, HLA-DR) and natural killer (NK) cell antigens. The neoplastic cells most resembled NK cells because in addition to being CD3(-)/CD56(+) with germline TCR genes, these cells were CD25(+)/CD122(+)/granzyme B(+) and possessed the functional properties of immature NK cells. The unusual clinical presentation, immunophenotype, and functional properties of these neoplastic cells suggest that this malignancy may be derived from the putative myeloid-NK precursor cell. Furthermore co-expression of NK and ALCL features supports the concept that a minority of null-ALCL may be derived from NK cells and expands the spectrum of phenotypes that can be seen in tumors produced by ALK fusion proteins. (Blood. 2001;98:1209-1216)

Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting.

Many patients with t(8;21) AML have residual positive cells during remission. We previously developed D-FISH probes that detect both derivative chromosomes and the normal alleles. In negative controls, only 2/44,000 (0.0045%) positive signals were observed. To investigate MRD, we examined specimens from 29 patients who had initially obtained CR. In remission patients, 61% had 1-4/2000 positive cells (0.05-0.19%). Higher frequencies were found in two patients in early relapse and in one patient in early remission. However, a negative test did not exclude relapse. Since false positives were negligible and because most t(8;21) AMLs express CD34, we asked whether cell sorting combined with FISH would increase the sensitivity. In one patient, we observed that 80% of CD34+ cells were t(8;21)+ at 2 months from initial clinical and cytogenetic remission. However, by 5 months the pre- and post-sorted populations contained 0.15% and 0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results are consistent with in vitro assays showing that residual t(8;21) cells undergo differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells.

Long-term results of the first 500 cases of acoustic neuroma surgery.

OBJECTIVE: This retrospective study focuses on 2 outcome results after surgical intervention for acoustic neuroma: (1) facial nerve status, and (2) hearing preservation. STUDY DESIGN: A total of 484 patients with an acoustic neuroma. RESULTS: Postoperative facial nerve outcomes were significantly different (P < 0.001) according to the size of the tumors. Tumor size had even more influence on the immediate postoperative results. In addition, statistical significance (P < 0.05) was demonstrated in comparing facial nerve outcomes with the surgeon's surgical experience. We also noted that as the patient's age increases, the likelihood for facial dysfunction may increase for all postoperative intervals. The overall success rate of retaining useful hearing was 27% (26 of 95). Class A hearing was retained in 66% (10 of 15) of cases operated on through middle fossa approach in the last 5 years. CONCLUSION: This study demonstrates that tumor size and surgeon's experience are the most significant factors influencing the facial nerve status and hearing outcome after removal of acoustic neuroma.

Direct electrochemical characterization of hyperthermophilic Thermococcus celer metalloenzymes involved in hydrogen production from pyruvate.

The reduction potentials of the metalloproteins pyruvate ferredoxin oxidoreductase (POR), ferredoxin, and hydrogenase isolated from hyperthermophilic Thermococcus celer (Topt = 88 degrees C) were determined as a function of temperature from 10 to 85 degrees C. Square-wave voltammetry experiments were carried out on 15 microL samples directly at an unmodified "edge-polished" pyrolytic graphite electrode using MgCl2 as an electrode promoter. POR exhibited two voltammetric waves with peaks at -280 and -403 mV at room temperature, indicating multiple redox centers, and a single wave at -420 mV at 85 degrees C. These waves displayed different temperature-dependent peak positions and peak heights, indicating that these redox centers have different thermodynamic and kinetic properties. Ferredoxin displayed a single linear temperature-dependent voltammetric wave at -280 mV at room temperature and -327 mV at 85 degrees C. Hydrogenase displayed a single biphasic temperature-dependent voltammetric wave at -197 mV at room temperature and -211 mV at 85 degrees C. Thermodynamic parameters associated with electron transfer, namely standard enthalpies and entropies for the redox centers in the various proteins, are reported.

TEL-AML1 fusion identifies a subset of children with standard risk acute lymphoblastic leukemia who have an excellent prognosis when treated with therapy that includes a single delayed intensification.

The Children's Cancer Group (CCG) found that children with moderate risk acute lymphoblastic leukemia (ALL) had an improved 5-year event-free survival (EFS) rate when treated with therapy that included a doubled delayed intensification (DDI) vs a single DI (SDI) phase. Because of increased toxicity with DDI, it is important to determine whether subgroups of children with ALL can be identified who have excellent outcomes with SDI therapy. TEL-AML1 fusion and hyperdiploid DNA content are present in the leukemic blasts of significant proportions of children with ALL and have been associated with an excellent prognosis. In this study, we retrospectively examined the impact of TEL-AML1 status and ploidy on treatment outcome in a cohort of 75 children with standard risk ALL treated at our institution between 1983 and 1993 with SDI therapy. TEL-AML1 fusion was present in 19/43 (44%) evaluable cases. Fifteen of 56 (27%) evaluable cases were classified as hyperdiploid based on a modal chromosome number of >/=51 and/or a DNA index of >/=1.16. The 7-year EFS was 81% for the 19 TEL-AML1-positive patients vs 54% for the 24 TEL-AML1-negative patients (P = 0.0264). In multivariate analyses, TEL-AML1-positive status was associated with a superior EFS (P = 0.02) even when the intial white blood count was included in the model. Overall survival (OS) at 7 years for TEL-AML1-positive patients was 100% vs 83% for TEL-AML1-negative patients (P = 0.0677). There were no differences in 7-year EFS or OS based on ploidy comparisons. These results underscore the need to examine closely the effects of treatment intensification on specific biologically defined subgroups of children with ALL.

Acquisition of p16(INK4A) and p15(INK4B) gene abnormalities between initial diagnosis and relapse in children with acute lymphoblastic leukemia.

Although numerous somatic mutations that contribute to the pathogenesis of childhood acute lymphoblastic leukemia (ALL) have been identified, no specific cytogenetic or molecular abnormalities are known to be consistently associated with relapse. The p16(INK4A) (p16), which encodes for both p16(INK4A) and p19(ARF) proteins, and p15(INK4B) (p15) genes are inactivated by homozygous deletion and/or p15 promoter hypermethylation in a significant proportion of cases of childhood ALL at the time of initial diagnosis. To determine whether alterations in these genes play a role in disease progression, we analyzed a panel of 18 matched specimen pairs collected from children with ALL at the time of initial diagnosis and first bone marrow relapse for homozygous p16 and/or p15 deletions or p15 promoter hypermethylation. Four sample pairs contained homozygous p16 and p15 deletions at both diagnosis and relapse. Among the 14 pairs that were p16/p15 germline at diagnosis, three ALLs developed homozygous deletions of both p16 and p15, and two developed homozygous p16 deletions and retained p15 germline status at relapse. In two patients, p15 promoter hypermethylation developed in the interval between initial diagnosis and relapse. In total, homozygous p16 deletions were present in nine of 18 cases, homozygous p15 deletions in seven of 18 cases, and p15 promoter hypermethylation in two of eight cases at relapse. These findings indicate that loss of function of proteins encoded by p16 and/or p15 plays an important role in the biology of relapsed childhood ALL, and is associated with disease progression in a subset of cases.

Different patterns of homozygous p16INK4A and p15INK4B deletions in childhood acute lymphoblastic leukemias containing distinct E2A translocations.

The p16INK4A (p16) and p15INK4B (p15) tumor suppressor genes are inactivated by homozygous gene deletion and p15 promoter hypermethylation in a significant proportion of childhood acute lymphoblastic leukemias (ALLs). However, little is known about the potential association between p16/p15 gene alterations and specific genetic abnormalities implicated in leukemogenesis. The t(1;19)(q23;p13) and t(17;19)(q21-22;p13) are non-random translocations observed in childhood ALL that create distinct E2A fusion proteins: E2A-PBX1 and E2A-HLF, respectively. Previously, a negative association was found between the t(1;19) and homozygous p16/p15 deletions. In this study we determined p16 and p15 gene status in additional t(1;19)+ ALLs and compared this incidence to that observed in t(17;19)+ ALLs. No homozygous p16 or p15 deletions were observed among 13 t(1;19)+ ALLs analyzed. In contrast, homozygous deletions of both p16 and p15 were present in two of four t(17;19)+ ALLs. None of 10 t(1;19)+ ALLs contained p15 promoter hypermethylation. In contrast, one of the two t(17;19)+ ALLs that lacked p15/p16 homozygous deletions showed probable hemizygous p15 hypermethylation. We conclude that homozygous p16 and/or p15 deletions and p15 hypermethylation rarely accompany E2A-PBX1 fusion, but occur in concert with E2A-HLF fusion in a subset of t(17;19)+ ALLs. These findings suggest that there may be different modes of cooperative leukemogenesis in ALLs associated with different E2A fusion proteins.

Differential responsiveness to cocaine in C57BL/6J and DBA/2J mice.

The present study compared cocaine-induced hyperlocomotion and cocaine i.v. self-administration in DBA/2J and C57BL/6J mice. In the locomotor activity experiment, these strains were tested for hyperlocomotion after i.p. cocaine injection (0-60.0 mg/kg), using a Digiscan Animal Activity Monitoring System. In the cocaine i.v. self-administration experiment, they were compared for their ability to acquire and maintain cocaine self-administration in operant chambers with levers as the manipulanda. Animals were first trained to respond for food as a reinforcer (condensed milk solution); they were then submitted to surgical i.v. insertion of an in-dwelling catheter, and required to respond for i.v. cocaine (0.25-4.0 mg/kg per injection) as a reinforcer. DBA/2J mice showed significantly higher maximal cocaine-induced hyperlocomotion, more rapid acquisition of cocaine self-administration, and significantly lower rates of cocaine self-administration. Cocaine concentration in the brains of DBA/2J and C57BL/6J mice failed to differ following i.p. injection, suggesting that distribution factors were not involved in the differential responses to cocaine. Although not conclusive, this pattern of effects may suggest that cocaine has greater reinforcing efficacy in DBA/2J mice, confirming genetic make-up as a determinant factor in cocaine taking behavior.

Intra-operative radiation therapy in pediatric neuroblastoma.

External beam irradiation (EBRT) has been shown to improve response rates and event-free survival in children with neuroblastoma and regional lymph node metastases. Irradiation during surgical exposure (intra-operative radiotherapy, IORT) with displacement of adjacent radiosensitive organs out of the treatment field allows for more precise delineation of the target volume and significantly reduces the amount of normal tissue exposed to irradiation. We have incorporated IORT into the treatment regimen of 24 children with neuroblastoma between the years of 1983-1991. IORT was directed to any residual tumor or the tumor bed; the median dose of radiation was 1,000 cGY, equivalent to 3,000 cGY of conventional EBRT. There were 11 males and 13 females. Two patients had stage II, 12 patients had stage III, and 10 patients had stage IV disease. Ten children received IORT for suspected recurrent or persistent neuroblastoma. Twelve patients were disease-free survivors following IORT with a median follow-up of 54 months. For those patients with stage III disease, seven children were disease-free survivors, while only three of 10 patients with stage IV disease survived (median follow-up 30 months). Disease-free Survival (DFS) correlated with the achievement of local tumor control in children with both stage III and IV neuroblastoma. There was limited morbidity and no episodes of obstructive uropathy were encountered. We conclude that IORT appears to be well tolerated and may have therapeutic benefit for a select group of patients with neuroblastoma. IORT merits future exploration by prospective study.

Cavernous lymphangioma presenting as a vaginal discharge in a six-year-old female: a case report.

STUDY OBJECTIVE: This case report is written to describe a new and unusual presentation of retroperitoneal cavernous lymphangioma. INTERVENTIONS: A large cystic abdominal mass was discovered during an examination under anesthesia to evaluate a vaginal discharge in a 6-year-old girl. The mass was diagnosed by computed tomography (CT) and removed via laparotomy with argon beam coagulation of smaller cystic lesions. RESULTS: Six months postoperatively, the patient had a negligible amount of vaginal discharge. CONCLUSIONS: Cavernous lymphangioma should be considered as a rare cause of vaginal discharge in young females.

Cessation of antibiotics regardless of ANC is safe in children with febrile neutropenia. A preliminary prospective trial.

PURPOSE: This study was designed to evaluate the safety and efficacy of stopping antibiotic treatment regardless of absolute neutrophil count (ANC) or signs of impending neutrophil recovery in children with febrile neutropenia (FN) and no identifiable infectious source. PATIENTS AND METHODS: Thirty-two consecutive cases of FN without identifiable source were prospectively evaluated. Patients were examined, cultured, and initially treated with ceftazidime +/- vancomycin. Antibiotics were discontinued and patients discharged regardless of ANC (WBC/microliter x [% segs + bands]) once all the following criteria were met: afebrile > or = 24 h; cultures negative at 48 h; thermometer and telephone available at home. Prompt notification of fever (T > 38.3 degrees C) and readmission were required. RESULTS: Median ANC was 60/microliters on admission and 160/microliters at discharge. Median length of treatment was 3 days. Four patients were readmitted for FN, and two patients were readmitted afebrile for cultures which became positive after discharge. None of the 32 cases suffered apparent complications from early discharge. CONCLUSION: Results of this preliminary trial suggest that cessation of antibiotics regardless of ANC is safe in cases of FN without identifiable source, provided that marrow is not infiltrated and that recurrent fever receives prompt antibiotic retreatment.

Safety and effect of transforming growth factor-beta(2) for treatment of venous stasis ulcers.

Transforming growth factor-beta(2) promotes healing in a variety of animal models and exhibits clinical effects thought to be mediated by connective tissue formation. Two clinical trials were conducted to evaluate the safety and effect of transforming growth factor-beta(2) purified from bovine bone and delivered topically to venous stasis ulcers three times per week for up to 6 weeks by means of a lyophilized collagen vehicle. The first was an open-label trial comparing transforming growth factor-beta(2) purified from bovine bone (0.5 microg/cm(2)) with a placebo consisting of lyophilized collagen vehicle-without active drug. After no safety issues arose in that trial, a prospectively randomized, closed-label, observer-blinded, three-armed trial was conducted to compare bovine transforming growth factor-beta(2) (2.5 microg/cm(2)) with the collagen matrix placebo vehicle and with a standard dressing. Standardized elastic compression was applied to all test extremities. The rate of reduction of ulcer area as measured by planimetry was the primary measure of effect. No serious safety-related events occurred in either trial. Clinical evaluation suggested that improvement in the quality and quantity of granulation tissue appeared to precede epithelialization of ulcers treated with bovine transforming growth factor-beta(2). In both studies, treatment with bovine transforming growth factor-beta(2) appeared to have a positive effect on the rate of ulcer closure, whereas ulcers in the control groups continued to exhibit impaired healing. In the open-label study, the mean rate of closure of ulcers treated with bovine transforming growth factor-beta(2) was significantly greater than that of ulcers treated with placebo. There was likewise enhanced reduction in ulcer area in the ulcers treated with bovine transforming growth factor-beta(2) in the second trial. However, because of a higher variability in patient response and a greater placebo effect, the difference was not significant. The placebo was not worse than the standard care arm, thereby showing that the vehicle is not injurious to healing. The combined results of the two trials suggest that, at doses of 0.5 to 2.5 microg/cm(2), bovine transforming growth factor-beta(2) is safe as a topically applied agent in a collagen matrix vehicle and can have a positive effect on closure of venous stasis ulcers. Large multicenter trials appear to be indicated to evaluate fully the potential utility of transforming growth factor-beta(2) in accelerating closure of chronic dermal ulcers.

Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Childrens Cancer Group study.

PURPOSE: The objectives of this study were to determine if the addition of etoposide, thioguanine, and dexamethasone to daunorubicin and cytarabine (five-drug regimen) during induction would improve remission induction rates and survival of children with acute myeloid leukemia (AML) when compared with the standard regimen of cytarabine and daunorubicin (7 + 3) and whether allogeneic bone marrow transplantation (BMT) or intensive chemotherapy consolidation with or without maintenance would give a superior outcome. PATIENTS AND METHODS: A total of 591 assessable children with AML entered Childrens Cancer Group (CCG) trial 213 between January 1986 and February 1989. The status of patients as of September 1, 1992 forms the basis of this report. The results were compared with previous AML studies. RESULTS: The projected survival rate of all patients at 5 years is 39% (event-free survival [EFS] rate, 31%), which is superior to that of the prior CCG study (P = .01). The induction rate was 79% for 7 + 3 and 76% for the five-drug regimen (not significant). Comparisons of BMT to chemotherapy favored BMT, but these differences do not always reach statistical significance (eg, 5-year disease-free survival [DFS] rate, 46% v 38% [P = .06] with donor available and 54% v 37% [P = .002] if treated according to protocol intent). No benefit for maintenance therapy was found and, in some comparisons, it was inferior to discontinuation of therapy (5-year survival rate, 46% v 68%, P < .01). CONCLUSION: The 5-year EFS rate of patients with AML is 31% and has improved. The five-drug induction regimen is no better than standard induction, BMT appears superior to chemotherapy, and maintenance therapy was not beneficial.