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Background: Infant acute lymphoblastic leukemia (ALL) is an infrequent disease characterized by clinical and biological features related to poor prognosis. Adapted therapies were designed without a clear consensus regarding the best treatment options. We aimed to compare the outcome between infant ALL cases receiving Interfant versus BFM-based protocols., Procedure: This is a retrospective observational study. From April 1990 to June 2018, infant ALL cases were enrolled in one of the five consecutive treatment protocols. Clinical, demographic, and biological features and outcome were evaluated. A comparative analysis was performed between Interfant protocols and BFM-based protocols., Results: During the studied period, 1913 ALL patients were admitted and 116 (6%) were infants. Treatment administered was: ALL-BFM'90 (n = 16), 1-ALL96-BFM/HPG (n = 7), Interfant-99 (n = 39), Interfant-06 (n = 35), and ALLIC-BFM'2009 (n = 19). The 5-year event-free survival probability (EFSp) was 31.9(standard error [SE] 4.6)% for the entire population, with a significant difference among risk groups according to Interfant-06 criteria (P = .0029). KMT2A-rearrangement status was the strongest prognostic factor (P = .048), independently of the protocol strategy. The median time for relapse was 24.1 months for patients with minimal residual disease (MRD)-negative versus 11.5 months for those with MRD-positive (P = .0386). EFSp and cumulative relapse risk probability (CRRp) were similar. Interfant protocols showed comparable induction (8.1% vs 7.1%, P = .852) and complete remission mortality (21.6% vs 28.6%, P = .438), failing to reduce the relapse rate (48.5% vs 30.7%, P = .149)., Conclusions: Interfant protocols and BFM-based protocols presented comparable results. The risk group stratification proposed by Interfant-06 was validated by our results, and MRD seems useful to identify patients with an increased risk of early relapse., (© 2020 Wiley Periodicals LLC.)

Introduction: Children with Down syndrome (DS) more commonly have acute lymphoblastic leukemia (ALL) and a lower survival rate than those without Down syndrome (WDS). We analyzed the clinical, demographic, and biological characteristics and treatment response of children with DS-ALL versus those WDS-ALL. Patients and methods: Patients with ALL between January 1990 and November 2016. The demographic and biologic characteristics and treatment response were compared using the χ² and Wilcoxon rank-sum tests. The overall survival and event-free interval (EFI) were analyzed using the Kaplan-Meier and log-rank tests., Results: 1795 patients were included; 54 had DS. Patients with DS-ALL were older (p= 0.0189). All had B-cell precursor immunophenotype and a lower incidence of recurrent abnormalities (p < 0.0001). They showed a better response rate to prednisone (p= 0.09) and a higher mortality in induction and complete remission (p < 0.0001). All deaths of patients with DS-ALL were treatment-related. The event-free survival (EFS) was 47% (± 8%) versus 73% (± 1%) (p= 0.006) and the EFI was 54% (± 9%) versus 75% (± 1%) (p= 0.0297) among patients with DS-ALL versus those WDS-ALL, respectively. The rate of relapse was similar in both groups (p= 0.6894). The EFI of patients with DS-ALL was lower in the group aged 6-9 years: 39% (± 19%) (p= 0.7885)., Conclusions: A lower survival was observed among children aged 6-9 years with DS-ALL. Although these children showed a better early response, their EFS and EFI were lower due to treatment-related mortality., (Sociedad Argentina de Pediatría.)

Eighty percent of children with acute lymphoblastic leukemia (ALL) survive with current treatments. Neurotoxicity is an infrequent adverse event. We describe clinical presentations of neurological toxicity, phases of treatment when these adverse events were more frequent and patients ́ outcome. From January-1995 to December-2015, 1379 ALL cases were admitted. Neurotoxicity was diagnosed in 49 patients (3.6%) and classified according to neurological syndromes. Medical records, laboratory-tests and images were reviewed. The diagnosed syndromes were: a) Methotrexate-leukoencephalopathy (MLE) (35.4%); b) Cerebral-venous-sinus thrombosis following L-Asparaginase administration (26.5%); c) Vincristine-induced-vocal-cord paralysis (VVCP) (14.2%); d) Stroke-associated vasospasm (14%), after high-dose methotrexate e) Severe polyneuropathy (6.1%); f) Methotrexate myelopathy (2%); and g) Pseudotumor-cerebri (2%) associated with corticosteroid therapy. Neurotoxicity was diagnosed during induction in 55% of cases. We conclude that MLE was the most frequent syndrome. VVCP was observed in infants and Down patients. Seizure was the most common symptom and toxicity occurred mainly during induction phase., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Prospective analysis of clinical characteristics and long-term treatment results of a pediatric cohort with Hodgkin lymphoma (HL) treated in a single institution with ABVD and restricted radiotherapy (RT)., Patients and Methods: Between September 2000 and December 2015, 165 new consecutive assessable patients with HL were registered at our institution. Lymphocyte predominant nodular HL was excluded. Low risk (LR) patients were stage I and IIA (no bulky disease, <4 involved ganglionar areas and no lung hilar nodes), high risk (HR) was assigned to stage IV and any other stage with bulky mediastinum. The rest of the cohort was treated as intermediate risk (IR). Chemotherapy for LR and IR patients was 4 and 6 courses of ABVD regimen, respectively. These subsets received Low-dose involved field radiotherapy only in case of partial remission at the end of chemotherapy (21 Gy in initially involved areas, plus 14 Gy boost on residual disease). The HR group was treated with 6 courses of ABVD followed always with 21 Gy involved field radiotherapy if complete remission (CR) was achieved. A boost of 14 Gy was added to residual disease in case of partial remission., Results: Median age was 10.6 years (range, 2.7 to 17 y). Males: 117 (71%); females: 48 (29%). Eighteen (11%) patients were stage I, 76 (46%) stage II, 35 (21%) stage III, and 35 (21%) stage IV. Forty-nine (30%) patients were assigned to LR, 49 (30%) to IR, and 67 (40%) to HR. Forty-three patients (26%) had "bulky" mediastinum involvement. One hundred thirty (79%) patients achieved CR after chemotherapy and 161 (98%) after RT. Four patients (all HR), did not respond to initial therapy and died of disease. One patient died in first CR due to adenovirus infection on previously therapy-related damaged lungs. Seventeen (10%) patients relapsed and 13 of them remained in second CR after further therapy. Seventy-six (46%) patients could be spared from RT and cured of disease (88% of LR patients and 67% of IR patients). With a median follow-up of 5 years, event free and overall survival were 0.84 (SE: 0.03) and 0.95 (SE: 0.02), respectively. Overall survival according to risk group was 1 for LR, 0.93 for IR, and 0.85 for HR. Acute toxicity and late effects due to therapy were not significant., Conclusions: The strategy of avoiding RT for LR and IR patients that responded completely to ABVD chemotherapy achieved very good results. For the HR group, the combination of 6 cycles of ABVD and Low-dose involved field radiotherapy was efficacious with similar good results. Nearly half of the patients could be cured without RT.

Introduction: Childhood acute leukemias (AL) and lymphomas achieve good survival rates. However, second neoplasms (SN) are a devastating event., Methods: From August 1987 to December 2016, 34 of 3321 (1%) patients with diagnosis of AL or lymphoma developed SN. SN were AL (n=16), CNS tumors (n=5), endocrinal tumors (n=3), lymphomas (n=2), schwannoma (n=2) assorted sarcomas (n=4), retinal melanoma (n=1), and Vanek tumor (n=1). Median latency was 51 (range, 10 to 110) months for hematological malignancies and 119 (range, 25 to 236) months for solid tumors (P=0.001)., Results: A total of 33 patients with SN were treated taking into account cumulative doses of anthracyclines and radiotherapy. Twenty-three (67.6%) patients achieved complete remission (CR), 5 died early during therapy and 5 were refractory or partial responders. Six patients presented relapses of the SN and 1 died in CR. Seventeen patients remain alive in CR, with a median follow-up of 110 (range, 4 to 276) months., Conclusions: (1) The latency period was significantly longer for patients developing solid tumors than for those developing AL. (2) AL was the most frequent SN. (3) Our results strongly encourage giving standard therapy to SN, considering cumulative doses of previous treatment, since similar probabilities of surviving as "de novo" counterparts can be achieved.

Childhood acute myeloid leukemia (AML) achieves event-free-survival (EFS) rates of ∼50%. Double induction phase has been introduced for improving these results. Four consecutive protocols for AML treatment were evaluated to assess the impact of the addition of a second induction course in our setting. From January 1990 to January 2014, 307 evaluable AML patients were accrued. They were classified into low-risk (LR) and high-risk (HR) according to cytogenetic/molecular findings and response on day 15. The first two studies administered one induction cycle while the latter two protocols administered double induction. Relapse was the most frequent event and early-deaths were reduced by 50% in the last protocol. Statistically significant differences were observed when comparing EFS in LR and HR groups. Patients from both risk-groups who received double induction achieved significantly better outcome. EFS improved in protocols with double induction and early-deaths rate was decreased. Cytogenetic/molecular features and early-response were confirmed as prognostic factors.

Competing Interests: Authors' disclosures of potential conflicts of interest and contributions are found at the end of this article.The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Guillermo L. ChantadaNo relationship to discloseIra J. DunkelConsulting or Advisory Role: Bristol-Myers Squibb, Ipsen, Esai Research Funding: Bristol-Myers Squibb (Inst), Genentech (Inst), GlaxoSmithKline (Inst)Paula S. SchaiquevichNo relationship to discloseEdith L. GrynszpancholcNo relationship to discloseJasmine FrancisNo relationship to discloseAlejandro CecilianoNo relationship to disclosePedro A. ZubizarretaNo relationship to discloseAdriana C. FañdinoNo relationship to discloseDavid H. AbramsonNo relationship to disclose

Patients with Down's Syndrome have a higher risk of developing acute megakaryoblastic leukemia (AML). Ten per cent of newborn infants with this syndrome have transient abnormal myelopoiesis (TAM), indistinguishable from AML, which generally remits spontaneously. A high incidence of GATA-1 gene mutations was described in both groups of patients. Fourteen bone marrow DNA samples (10 ATM/4 AML) were analyzed by PCR and sequencing; these samples were obtained from 13 patients with Down's Syndrome to describe the rate and mutation characteristics of the GATA-1 gene in the studied population and its consequences at a protein level. Mutations were detected in 10 out of 10 TAM and in 3 out of 4 AML, which at a protein level would result in an early termination codon (n= 5), alterations in the splicing site (n= 6) or sequence change (n= 3). The high rate of GATA-1 gene mutations was confirmed in newborn infants with Down's Syndrome and MAT or AML.

Although rarely, switches between lymphoid and myeloid lineages may occur during treatment of acute leukemias (AL). Correct diagnosis relies upon confirmation by immunophenotyping of the lineage conversion and certification that the same cytogenetic/molecular alterations remain despite the phenotypic changes. From a total of 1,482 AL pediatric patients, we report nine cases of lineage conversion (0.6%), seven from lymphoid (four Pro-B, two Pre-B, one Common) to myelo-monocytic, and two from myeloid (bilineal, with myeloid predominance) to Pro-B. Eight patients were infants. Switches were suggested by morphology and confirmed with a median of 15 days (range: 8 days-6 months) from initiation of therapy. Of note, in five cases switches occurred before day 15. Stability of the clonal abnormalities was assessed by cytogenetic, RT-PCR/Ig-TCR rearrangement studies in all patients. Abnormalities in 11q23/MLL gene were detected in seven cases. Treatment schedules were ALL (two pts), Interfant-99 (five pts) and AML (two pts) protocols. Despite changing chemotherapy according to the new lineage, all patients died. Our findings support the association of lineage switches with MLL gene alterations and the involvement of a common lymphoid B-myeloid precursor. New therapies should be designed to address these rare cases. Possible mechanisms implicated are discussed., (Copyright © 2012 Wiley Periodicals, Inc.)

The present study was performed to establish the prevalence of the recurrent fusion transcripts in Argentinean pediatric patients with acute lymphoblastic leukemia (ALL). A total of 380 newly diagnosed children (including 50 infants and 44 T-ALL) were screened by RT-PCR; the incidence of recurrent rearrangements was: ETV6-RUNX1, 12.9%; TCF3-PBX1, 5.0%; BCR-ABL1, 1.6%; and MLL rearrangements, 10.5%. STIL-TAL1 was detected in 22.7% of T-ALL cases. In B-ALL cases, the pEFS was significantly influenced by the presence of genetic alterations. RT-PCR studies improved patients' stratification and also the overall outcome of children treated in a pediatric hospital from a developing country., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Our aim was to compare two different schedules of maintenance in pediatric acute lymphoblastic leukemia (ALL) treated with a BFM-based therapy, in a randomized study: an Arm with 6-MP + MTX (with or without vincristine and dexamethasone pulses) versus a more intensive continuation phase., Procedure: From January 1996 to November 2002, 429 eligible children with ALL were enrolled in a protocol with BFM-based back-bone, followed by a randomized continuation phase in standard (SRG) and intermediate (IRG) risk groups. Patients were randomized between Arms A and B for SRG and B or C for IRG. Arms A and C consisted of 6-MP and MTX and in Arm C, six pulses of VCR and dexamethasone were added. Arm B combined four pairs of drugs rotated weekly. All risk-groups received maintenance until completing 2 years of therapy from diagnosis., Results: With a median follow-up of 138 (range: 96-178) months, the overall pEFS (SE) was 72 (6)% for all patients and the different risk groups showed: SRG: 85 (3)%, IRG: 71 (1)%, and HRG: 42 (7)% (P-value ≤ 0.0001). The pDFS (SE) according to the assigned arm of maintenance was, for Arm A: 89 (3)% and for Arm B: 85 (4)% in SRG, and, for Arm B: 77 (4)% and for Arm C: 75 (4)% in IRG, at 10 years follow-up. There were no statistically significant differences in outcome between arms of maintenance for both risk groups., Conclusions: In protocols with initial BFM-based strategy, a more intensive continuation phase did not benefit any risk group of patients., (Copyright © 2011 Wiley-Liss, Inc.)

Historically, t(1;19)(q23;p13.3) has been related to pre-B acute lymphoblastic leukemia (ALL) and associated with a poor prognosis. Current treatments have overcome this dismal outcome, but advantages in survival for the unbalanced group have been reported. We compared the outcome of balanced and unbalanced der(19)t(1;19) cases and also patients with t(1;19)/TCF3-PBX1 versus patients without this translocation, to assess its prognostic value. From January 1990 to December 2010, t(1;19)(q23;p13)/TCF3-PBX1 was detected in 48 cases. Patients were treated with Berlin-Frankfurt-Münster (BFM)-based protocols and classified into balanced (n = 17) and unbalanced (n = 23) groups. The probability of event-free survival (pEFS) (standard error) of patients with t(1;19)/TCF3-PBX1 was 85% (6%), for the unbalanced group 78% (10%), and 88% (8%) for the balanced. The pEFS of patients with t(1;19)/TCF3-PBX1 was significantly superior to that of patients without t(1;19)/TCF3-PBX1 (p-value <0.0001). Patients with t(1;19)/TCF3-PBX1 presented a good outcome with no differences between balanced and unbalanced subgroups. Thus, risk-adjustment therapy would not be necessary for cases with t(1;19)/TCF3-PBX1.

Purpose: To assess the value of initial peripheral blast count in patients with acute lymphoblastic leukemia (ALL) and prednisone good response (PGR)., Patients and Methods: From January 1990 to December 1995, 403 consecutive patients with newly diagnosed ALL were enrolled in the authors' protocol 1-ALL90-BFM/HPG. Prednisone good response was defined as a blast count of less than 1,000/microL and a prednisone poor response (PPR) as a blast count of at least 1,000/microL, both in peripheral smears, after 7 days of oral prednisone (60 mg/m2 per day) and one intrathecal dose of methotrexate. In the PGR group, patients were divided into two subgroups: patients who had less than 1,000 blasts/microL at diagnosis and those with at least 1,000 blasts/microL at diagnosis., Results: Three-hundred thirty-seven patients (90%) had PGR and 37 had (10%) PPR. At 5-year follow-up, event-free survival estimates were 67 +/- 3.8% and 38 +/- 8% for PGR and PPR, respectively (P = 0.0001). In the PGR group, 114 patients (34%) had an initial blast count of less than 1,000/microL and 223 (66%) had an initial blast count of at least 1,000/microL. The authors compared the clinical and laboratory characteristics of these subgroups at diagnosis and outcome and detected significant differences in white cell count, incidence of T immunophenotype, and presence of mediastinal or spleen enlargement. However, there were no differences in response to induction treatment, death in complete remission, relapses, or event-free survival probability., Conclusions: In the PGR group, regardless of the initial blast count, both subgroups had the same outcome. The PGR group with an initial blast count of at least 1,000/microL had significantly higher white cell counts. T markers, and mediastinal or spleen enlargement at diagnosis. Response to prednisone is a practical, inexpensive, and good prognostic factor in childhood ALL.

Background: A high cure rate may be attained for locally advanced, undifferentiated nasopharyngeal carcinoma (NPC) in children, provided that a combined modality of treatment is employed. Both local and systemic therapies are necessary. Results at a single pediatric institution were analyzed., Methods: From November 1988 to December 1997, 16 consecutive patients were treated with NPC at the Hospital Garrahan in Buenos Aires, Argentina. The authors were able to evaluate 11 patients (9 boys and 2 girls); their median age was 12 (range, 8-14) years. Chemotherapy consisted of 3 courses, every 3 weeks, of 5-fluorouracil (500 mg/m(2)) plus bleomycin (15 mg/m(2)) daily for 4 days, with cisplatin (100 mg/m(2)) added the last day. External beam radiotherapy was delivered over a median of 52 (range, 45-63) days, to a median cumulative dose to the primary site of 55 (range, 50-61.2) grays (Gy). The median dose for the lower neck area was 45 (range, 45-55.8) Gy. All patients received radiotherapy to the primary site and to the initially involved lymphoid areas, with daily single doses of 1.8 Gy (5 of 7 days per week)., Results: The main symptoms at onset were cervical mass (100%), epistaxis (54%), cephalalgia (36%), and trismus (36%). All cases were Stage IV (American Joint Committee on Cancer and International Union Against Cancer TNM system). Complete response was achieved in 45% of patients after initial chemotherapy. With a median follow-up of 63 (range, 23-119) months, disease free survival (with standard error [SE]) and overall survival estimates were 61% (16%) and 91% (9%), respectively, at 75 months. Acute toxicity due to therapy was tolerable. Chronic sinusitis (73%), hypothyroidism (73%), and mild (64%) or moderate (9%) neck fibrosis were detected at follow-up., Conclusions: Although this series is small, the authors concluded that NPC patients have a good chance of survival in the setting described, in spite of locally advanced disease. Chemotherapy might be useful in preventing the development of systemic metastases., (Copyright 2000 American Cancer Society.)

Background: Febrile neutropenia is a heterogeneous condition. Recently, several risk factors have been defined, permitting the definition of a lower risk group of patients who may benefit form less aggressive therapy. The use of an oral antibiotic approach was tested in the current trial., Methods: From May 1997 to March 1998, 154 episodes of lower risk febrile neutropenia in 128 children with a mean age of 62 (range, 8-200) months were enrolled in this randomized, single-institution trial. Inclusion criteria were fever (> 38 degrees C), neutropenia (absolute neutrophil count < 500/mm(3)), lower risk features (i.e., absence of severe comorbidity factors, good clinical condition, negative blood cultures, control of local infection, no fever during the last 24 hours), and compliance of parents. After 3 days of ceftriaxone (100 mg/kg/day administered intravenously [i.v.]) every 12 hours plus amikacin (15 mg/kg/day i.v.) every 24 hours for 3 days, all patients were discharged and randomized to be allocated to 2 treatment arms. Group A (n = 74) received ceftriaxone cefixime (8 mg/kg/day administered orally) every 24 hours for 4 days, whereas Group B (n = 80) was treated with ceftriaxone plus amikacin for 7 days. Failure was defined as the need for second hospitalization during the same episode of neutropenia, or fever during the 7 days after discharge., Results: Most of the patients (49% in Group A and 55% in Group B) had acute leukemia. Fifty-four (72%) children in Group A and 46 (56%) in Group B had fever of unknown origin (P = not significant [NS]). No significant differences were found in the sites of initial infection between the two groups. Overall results were outstanding, with a favorable outcome in 73 of 78 cases (98.6%) in Group A and 78 of 80 cases (97.5%) in Group B (P = NS). Three patients needed a second hospitalization due to failure of the initial therapy: one in Group A and two in Group B. All three did well with secondary treatment., Conclusions: In lower risk febrile neutropenic children receiving anticancer therapy, the efficacy of oral cefixime, given for 4 days after 72 hours of intravenous ceftriaxone plus amikacin, was similar to that of 7 days of parenteral ceftriaxone plus amikacin. The oral outpatient therapy approach to the treatment of lower risk febrile neutropenia after chemotherapy is safe and may be cost-saving. This strategy might be adopted as standard therapy in the future., (Copyright 2000 American Cancer Society.)

Background: The association between t(8;21) and granulocytic sarcoma (GS) is well known, but to the authors' knowledge the prognostic significance of GS in these patients has not been defined clearly., Methods: Between January 1990 and July 1999 174 children with acute myeloid leukemia were admitted to the study institution. Translocation (8;21) was identified in 20 patients (11.5%). Eighteen patients were evaluable for the current study and 8 presented with GS at the time of diagnosis (GS+)., Results: The authors defined two groups of patients: those who were GS+ and those who were GS-. One patient in the GS+ group and two patients in the GS- group died during the induction phase of the study. Complete remission was achieved in seven patients in the GS+ group and eight patients in the GS- group. Two patients developed a recurrence in the GS+ group as did one patient in the GS- group. The event free-survival probability (the standard error) was 58% (18%) in the GS+ group and 70% (14%) in the GS- group. Localization of GS was in only one site in seven patients and at multiple sites in one patient. Patients with an epidural mass received local radiotherapy (one patient) or surgery (two patients). Two of these patients developed paraplegia as sequelae: one patient after surgery and one patient after radiotherapy. One patient with orbital GS received local radiotherapy because of progressive proptosis. The remaining four patients had a complete resolution of the GS with chemotherapy only., Conclusions: In the current study of patients with t(8;21)(q22;q22), the presence of granulocytic sarcoma was not found to be an adverse prognostic factor. However, careful attention should be paid, especially to patients with an epidural site, to avoid sequelae. Chemotherapy appears to be the optimum treatment for these children., (Copyright 2000 American Cancer Society.)

From January 1990 to August 1997, 29 consecutive patients were treated with newly diagnosed primary acute promyelocytic leukemia (APL) at the authors' Institution. Of these, 27 (16 boys and 11 girls) were evaluable. Median age at diagnosis was 6.3 (range: 1.9-15.7) years. This population was treated with two consecutive protocols: 13 patients were included in the AML-HPG-90 protocol and 14 in the AML-HPG-95. The initial treatment was the same for both protocols: an induction 8-day phase with cytarabine, idarubicin, and etoposide was followed by a consolidation with cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, doxorubicin, and prednisone. Two courses of intensification with high-dose (HD) cytarabine and etoposide were given in the first study. Only one intensification course was administered in the second study, with HD cytarabine plus idarubicin or etoposide decided by randomization. Complete remission was achieved in 67% (18/27) of cases. Mortality on induction was quite high, 30% (8/27) mainly due to hemorrhages from disseminated intravascular coagulation (DIC). The event-free survival estimate for all patients was 0.47 (SE: 0.1). From April 1994, all-trans-retinoic acid (ATRA) was administered just during the first days of the induction phase (median: 9, range: 2-27) to stop or prevent DIC. Eighteen patients received ATRA and 9 did not. Three patients developed signs of ATRA syndrome during the first days of administration but no one died due to this toxicity. The impact of a short course of ATRA on early control of DIC was studied by analyzing the number of platelet, cryoprecipitate, and fresh frozen plasma transfusions during the induction phase in both groups. No statistical differences in complete remission rate, early mortality, need of transfusion of blood components for DIC, and survival estimates could be established between patients who received ATRA and those who did not. ATRA used in a short-course schedule during induction of APL did not stop early mortality due to DIC. Moreover, survival results did not improve with this method of ATRA usage. Longer periods of ATRA administration during APL therapy are strongly recommended.

We describe an 8 year old boy who had received chemotherapy for an acute promyelocytic leukemia and developed a secondary leukemia 27 months after the diagnosis of this first malignancy. Blasts cells were positive for cytoplasmic markers CD22, CD3 and myeloperoxidase. Cell surface T and myeloid-associated markers were also detected. Cytogenetic study disclosed monosomy 7. The patient achieved complete remission, but relapsed 15 months later with identical immunophenotypic and cytogenetic findings. Three-lineage commitment is proved by the expression of specific criteria for myeloid, and lymphoid T and B typing. A multipotent immature progenitor must be the target of leukemogenic agents. The prognosis is obviously ominous.

We report results achieved in our institution with an acute lymphoblastic leukaemia risk-oriented treatment trial opened in January 1990 and closed on December 1995. The study was similar to the German ALL-BFM'90, except for using Protocol III for the standard-risk group, 2 g/m2 of methotrexate in Protocol M, and preventive cranial irradiation for the high-risk group only. The high-risk group included mostly patients with prednisone poor initial response and/or adverse cytogenetic features. This analysis included 374 patients, whose mean age was 6 years (range: 1 month-17 years). The overall complete remission rate was 94.4% (353/374) and the 5-year event-free survival (standard error) probability is 64(5)%. The 5-year event-free survival estimates for each risk group were: (1) high-risk group 37(5)%; (2) intermediate-risk group 66(1)%; and (3) standard-risk group 74(4)% (P = 0.0001). There are significantly higher-rates of isolated bone marrow and testicular relapses in the high-risk subset of patients. Our dismal results and the published experience, lead us to conclude that the optimal treatment for these high-risk acute lymphoblastic leukaemia patients is not currently known.

Background: Acute myeloid leukemia (AML) is well-recognized as one of the most important second malignancies. We report the occurrence of secondary AML (sAML) in our institution., Procedure: From September 1987 to August 1996 we have observed sAML in 9 patients (median age 4 years), 5 of them previously treated for hematologic malignancies (group I): acute lymphoblastic leukemia (n = 2), AML (n = 1), non-Hodgkin lymphoma (n = 1). Hodgkin disease (n = 1), and 4 of these 9 patients treated for solid tumors (group II): neuroblastoma (n = 1), retinoblastoma (n = 1), Wilms tumor (n = 1), and central nervous system germinoma (n = 1)., Results: All the patients had topoisomerase II inhibitors as part of treatment of their first malignancy, but only 5 patients received epipodophyllotoxins. Alkylating agents were part of primary therapy in 8 of 9 patients. The latency period for the development sAML was 26.5 (range = 2-55) months. The morphologic FAB features of sAML were M5 (n = 5), M4 (n = 3), and M2 (n = 1). Cytogenetic studies showed r11q23 in 3 patients, all of them with prior hematological malignancies. Initial therapy for sAML in all cases was chemotherapy (including cytarabine in combination with idarubicin and etoposide or doxorubicin or mitoxantrone). Three patients died during induction and 6 achieved complete hematologic response. Three of these patients remain disease free at +15, +51, and +99 months post-remission (including one post allogeneic BMT). The remaining 3 patients died, 1 in complete remission one month after diagnosis and 2 relapsed and died with progressive disease (one post allogeneic BMT)., Conclusions: Secondary AML is a sequela of oncologic treatments with specific cytogenetic abnormalities and poor outcome. A few patients can achieve long-term survival even with standard chemotherapy.

Purpose: To report the feasibility and results of a study based on the BFM-ALL. NHL/86 protocol for B-non-Hodgin's Lymphoma (NHL) and B-Acute Lymphoblastic Leukemia (B-ALL) in Argentina. Design. Prospective, single arm, non-randomized trial., Patients and Methods: From August 1988 to December 1993, 87 consecutive patients with B-NHL/B-ALL were admitted and 82 were eligible. The therapy was stratified according to stage. All patients received a cytoreductive prephase with cyclophosphamide and prednisone. Those with stage I-II were treated with three 5-day blocks of combined intense chemotherapy including dexamethasone, cyclophosphamidie, ifosfamide, cytarabine, teniposide, doxorabicin, and 500 mg/m2 of methotrexate as a 24 hour continuous infusion. Stage III received 6 blocks and those with stage IV/B-ALL received 6 intensified blocks in which 2 g/m2 of 24 hour continuous infusion methotrexate and vincristine were added. Triple intrathecal therapy was given for CNS prevention. After the first two blocks the response was assessed and those with a partial response were offered optionallya second look surgery or local radiotherapy., Results: With a median follow-up of 38 (range 16-71) months, the event-free survival (pEFS) for the whole group was 0.69 (Stage I-II n = 16 pEFS = 0.94, stage III n = 50 pEFS = 0.66, Stage IV n = 7 pEFS = 0.43, B-ALL n = 9 pEFS = 0.66). Patients with stage III abdominal tumors who achieved a partial response by imaging studies after induction had a significantly higher risk of relapse than those with a complete response (p = 0.02). Relapse was the most frequent event Toxicity was mainly hematological., Conclusions: The application of this protocol was feasible in our setting and its results comparable to the German study. Patients with stage I-II had an excellent outcome. Those with stage III and B-ALL achieved an encouraging event-free survival, however those with abdominal tumors and partial response to induction chemotherapy fared less favourably. This strategy was less effective for patients with initial CNS disease.