We report results achieved in our institution with an acute lymphoblastic leukaemia risk-oriented... more 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.
Between July 1990 and December 1995, 111 new consecutive pediatric patients with acute myelogenou... more Between July 1990 and December 1995, 111 new consecutive pediatric patients with acute myelogenous leukemia (AML) have been treated in our institution. Eleven of them (9.9%) had Down's syndrome (DS), 6 boys and 5 girls. The median age was 22.5 (range 10-40) months. FAB subtypes were the following: M7: 6, M4: 3, and M0: 2. Five of them had previously had myelodysplasia and in 3, all FAB M7, myelofibrosis was detected. This population was treated with two consecutive protocols. Nine patients were included in the AML-HPG-90 protocol and 2 patients in the AML-HPG-95 study, respectively. However, all DS patients in this series received the same treatment. Eight patients achieved complete remission: two patients received two cycles of intensification with high dose (HD) ara-C, and 1 patient, only one cycle; the other 5 were prevented from receiving such therapy because of unacceptable toxicity or death. At 45 months, event-free survival and overall survival estimates were 0.30, S.E. 0.16. Mortality was remarkably high. All deaths (7) were associated with sepsis (5) or pulmonary infection (2). Three deaths occurred before achieving complete remission, 3 patients died during the consolidation phase and 1 died whilst off treatment. No one presented leukemic relapse. We conclude that this AML-BFM treatment strategy is highly toxic to children with DS and AML in our setting. Efforts will be made to improve clinical support and to administer less intensive therapy to this particular pediatric AML subgroup, which, in fact, has a better prognosis than the same non-trisomic population.
To assess the value of initial peripheral blast count in patients with acute lymphoblastic leukem... more To assess the value of initial peripheral blast count in patients with acute lymphoblastic leukemia (ALL) and prednisone good response (PGR). 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. 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. 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.
Our aim was to compare two different schedules of maintenance in pediatric acute lymphoblastic le... more 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. 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. 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. In protocols with initial BFM-based strategy, a more intensive continuation phase did not benefit any risk group of patients.
Acute myeloid leukemia (AML) is well-recognized as one of the most important second malignancies.... more 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. 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). 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). 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.
Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagn... more Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagnosis and successful treatment of childhood primary leptomeningeal lymphoma. Medical and Pediatric Oncology, 34: 361–363. doi: 10.1002/(SICI) 1096-911X (200005) ...
Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagn... more Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagnosis and successful treatment of childhood primary leptomeningeal lymphoma. Medical and Pediatric Oncology, 34: 361–363. doi: 10.1002/(SICI) 1096-911X (200005) ...
CD4+ CD56+ malignancies have only recently been related to dendritic cell (DC) lineage. The few c... more CD4+ CD56+ malignancies have only recently been related to dendritic cell (DC) lineage. The few cases described, mostly adults and elderly, typically present with cutaneous lesions, followed by disseminated tumor localizations within a few months, with a generally very aggressive course and fatal outcome, despite the different therapeutic approaches employing chemotherapy and/or radiotherapy. Considering that leukemias in childhood and in adults are different diseases, we describe three pediatric cases to help compare the biological characteristics, immunophenotype, clinical features, treatment response and incidence of this disease in both age groups. From a total 1363 new patients with acute leukemia (AL), we report three cases with blasts of French - American - British L2 morphology, an absence of the most specific markers for myeloid, T or B lineage and lacking CD34, which led us to evaluate the blasts with an extensive panel of antibodies, including those related to the other putative pathways of lymphoid differentation: natural killer and DC. The cells expressed CD4, CD56, HLA-DR, BDCA-2 and BDCA-4. None of our cases presented with skin involvement. All three children showed good response to acute lymphoblastic leukemia (ALL) protocols, achieving complete remission even when one of the patients relapsed and received an allogeneic transplant. These findings, in spite of the small number of patients, suggest that the clinical course in children might be less aggressive, and that regular ALL protocols would be effective. We emphasize the importance of including antibodies for DC lineage in cases of CD34(-) unclassifiable AL to further characterize these rare cases (0.22%), considering that the tumor cell affiliation to DC lineage relies exclusively on immunophenotypic criteria.
The association between t(8;21) and granulocytic sarcoma (GS) is well known, but to the authors&a... more 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. 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+). 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. 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.
The association between t(8;21) and granulocytic sarcoma (GS) is well known, but to the authors&a... more 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. 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+). 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. 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.
To compare prospective treatment strategies in childhood Hodgkin disease to the following subsets... more To compare prospective treatment strategies in childhood Hodgkin disease to the following subsets of patients: a) Favorable prognostic group: these patients were randomized to receive 6 vs. 3 CVPP chemotherapy cycles without radiotherapy (CVPP: cyclophosphamide, vinblastine, procarbazine, and prednisone. The scheme was repeated every 28 days). b) Intermediate prognostic group: these patients were randomized to receive 6 cycles of CVPP or AOPE (AOPE: Adriamycin, vincristine, prednisone, and etoposide). Between the third and fourth cycles, all patients in this group received radiotherapy (RT)(30-40 Gy to initially involved areas). c) Unfavorable prognostic group: those patients received a single arm regimen of 6 cycles of CCOPP/CAPTe (3 of each combination) every 28 days. All these patients received radiotherapy (30-40 Gy to initially involved areas). From October 1987 to December 1994, a total of 114 children and adolescents were evaluated. Mean age was 9 (range 2-17) years. There were 72 boys and 42 girls. With a median follow-up of 5 (range 1.5-8.7) years, at 80 months event-free survival (EFS) and overall survival (OS) for the whole cohort are 0.809 (SE: 0.04) and 0.873 (SE: 0.04), respectively (SE: Standard Error). Favorable prognostic group (n = 26) EFS is 0.831 (0.09) (Arm CVPP x 3:0.857 (0.13) and Arm CVPP x 6: 0.875 (0.08); p = non significant). Intermediate prognostic group (n = 64) EFS is 0.806 (0.05) (Arm CVPP x 6 + RT: 0.872 (0.05) and Arm AOPE x 6 + RT: 0.667 (0.10); p = 0.04). Unfavorable group (n = 24) EFS is 0.829 (0.07). Results of treatment for the whole group are satisfactory. However, 3 cycles of CVPP without radiotherapy obtain equal EFS than 6 cycles without radiotherapy in the favorable prognostic group. In the intermediate prognostic group, 6 cycles of CVPP plus radiotherapy obtain a superior EFS than 6 cycles of AOPE plus radiotherapy. With the success of treatment for Hodgkin disease in children, future research needs to be focused in reducing toxicity without altering the excellent actual outcome.
From January 1990 to August 1997, 29 consecutive patients were treated with newly diagnosed prima... more 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 report results achieved in our institution with an acute lymphoblastic leukaemia risk-oriented... more 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.
Between July 1990 and December 1995, 111 new consecutive pediatric patients with acute myelogenou... more Between July 1990 and December 1995, 111 new consecutive pediatric patients with acute myelogenous leukemia (AML) have been treated in our institution. Eleven of them (9.9%) had Down's syndrome (DS), 6 boys and 5 girls. The median age was 22.5 (range 10-40) months. FAB subtypes were the following: M7: 6, M4: 3, and M0: 2. Five of them had previously had myelodysplasia and in 3, all FAB M7, myelofibrosis was detected. This population was treated with two consecutive protocols. Nine patients were included in the AML-HPG-90 protocol and 2 patients in the AML-HPG-95 study, respectively. However, all DS patients in this series received the same treatment. Eight patients achieved complete remission: two patients received two cycles of intensification with high dose (HD) ara-C, and 1 patient, only one cycle; the other 5 were prevented from receiving such therapy because of unacceptable toxicity or death. At 45 months, event-free survival and overall survival estimates were 0.30, S.E. 0.16. Mortality was remarkably high. All deaths (7) were associated with sepsis (5) or pulmonary infection (2). Three deaths occurred before achieving complete remission, 3 patients died during the consolidation phase and 1 died whilst off treatment. No one presented leukemic relapse. We conclude that this AML-BFM treatment strategy is highly toxic to children with DS and AML in our setting. Efforts will be made to improve clinical support and to administer less intensive therapy to this particular pediatric AML subgroup, which, in fact, has a better prognosis than the same non-trisomic population.
To assess the value of initial peripheral blast count in patients with acute lymphoblastic leukem... more To assess the value of initial peripheral blast count in patients with acute lymphoblastic leukemia (ALL) and prednisone good response (PGR). 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. 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. 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.
Our aim was to compare two different schedules of maintenance in pediatric acute lymphoblastic le... more 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. 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. 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. In protocols with initial BFM-based strategy, a more intensive continuation phase did not benefit any risk group of patients.
Acute myeloid leukemia (AML) is well-recognized as one of the most important second malignancies.... more 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. 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). 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). 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.
Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagn... more Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagnosis and successful treatment of childhood primary leptomeningeal lymphoma. Medical and Pediatric Oncology, 34: 361–363. doi: 10.1002/(SICI) 1096-911X (200005) ...
Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagn... more Felice, MS, Zubizarreta, PA, Rossi, JG, Rose, A., Alfaro, EM and Sackmann-Muriel, F.(2000), Diagnosis and successful treatment of childhood primary leptomeningeal lymphoma. Medical and Pediatric Oncology, 34: 361–363. doi: 10.1002/(SICI) 1096-911X (200005) ...
CD4+ CD56+ malignancies have only recently been related to dendritic cell (DC) lineage. The few c... more CD4+ CD56+ malignancies have only recently been related to dendritic cell (DC) lineage. The few cases described, mostly adults and elderly, typically present with cutaneous lesions, followed by disseminated tumor localizations within a few months, with a generally very aggressive course and fatal outcome, despite the different therapeutic approaches employing chemotherapy and/or radiotherapy. Considering that leukemias in childhood and in adults are different diseases, we describe three pediatric cases to help compare the biological characteristics, immunophenotype, clinical features, treatment response and incidence of this disease in both age groups. From a total 1363 new patients with acute leukemia (AL), we report three cases with blasts of French - American - British L2 morphology, an absence of the most specific markers for myeloid, T or B lineage and lacking CD34, which led us to evaluate the blasts with an extensive panel of antibodies, including those related to the other putative pathways of lymphoid differentation: natural killer and DC. The cells expressed CD4, CD56, HLA-DR, BDCA-2 and BDCA-4. None of our cases presented with skin involvement. All three children showed good response to acute lymphoblastic leukemia (ALL) protocols, achieving complete remission even when one of the patients relapsed and received an allogeneic transplant. These findings, in spite of the small number of patients, suggest that the clinical course in children might be less aggressive, and that regular ALL protocols would be effective. We emphasize the importance of including antibodies for DC lineage in cases of CD34(-) unclassifiable AL to further characterize these rare cases (0.22%), considering that the tumor cell affiliation to DC lineage relies exclusively on immunophenotypic criteria.
The association between t(8;21) and granulocytic sarcoma (GS) is well known, but to the authors&a... more 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. 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+). 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. 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.
The association between t(8;21) and granulocytic sarcoma (GS) is well known, but to the authors&a... more 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. 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+). 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. 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.
To compare prospective treatment strategies in childhood Hodgkin disease to the following subsets... more To compare prospective treatment strategies in childhood Hodgkin disease to the following subsets of patients: a) Favorable prognostic group: these patients were randomized to receive 6 vs. 3 CVPP chemotherapy cycles without radiotherapy (CVPP: cyclophosphamide, vinblastine, procarbazine, and prednisone. The scheme was repeated every 28 days). b) Intermediate prognostic group: these patients were randomized to receive 6 cycles of CVPP or AOPE (AOPE: Adriamycin, vincristine, prednisone, and etoposide). Between the third and fourth cycles, all patients in this group received radiotherapy (RT)(30-40 Gy to initially involved areas). c) Unfavorable prognostic group: those patients received a single arm regimen of 6 cycles of CCOPP/CAPTe (3 of each combination) every 28 days. All these patients received radiotherapy (30-40 Gy to initially involved areas). From October 1987 to December 1994, a total of 114 children and adolescents were evaluated. Mean age was 9 (range 2-17) years. There were 72 boys and 42 girls. With a median follow-up of 5 (range 1.5-8.7) years, at 80 months event-free survival (EFS) and overall survival (OS) for the whole cohort are 0.809 (SE: 0.04) and 0.873 (SE: 0.04), respectively (SE: Standard Error). Favorable prognostic group (n = 26) EFS is 0.831 (0.09) (Arm CVPP x 3:0.857 (0.13) and Arm CVPP x 6: 0.875 (0.08); p = non significant). Intermediate prognostic group (n = 64) EFS is 0.806 (0.05) (Arm CVPP x 6 + RT: 0.872 (0.05) and Arm AOPE x 6 + RT: 0.667 (0.10); p = 0.04). Unfavorable group (n = 24) EFS is 0.829 (0.07). Results of treatment for the whole group are satisfactory. However, 3 cycles of CVPP without radiotherapy obtain equal EFS than 6 cycles without radiotherapy in the favorable prognostic group. In the intermediate prognostic group, 6 cycles of CVPP plus radiotherapy obtain a superior EFS than 6 cycles of AOPE plus radiotherapy. With the success of treatment for Hodgkin disease in children, future research needs to be focused in reducing toxicity without altering the excellent actual outcome.
From January 1990 to August 1997, 29 consecutive patients were treated with newly diagnosed prima... more 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.
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Papers by Elizabeth Alfaro