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F Sackmann-Muriel

Publications and source records attributed to F Sackmann-Muriel.

At least 19 recordsLinked to original sources

Childhood acute lymphoblastic leukemia: prognostic value of initial peripheral blast count in good responders to prednisone.

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.

Adolescent↗

Nasopharyngeal carcinoma in childhood and adolescence: a single-institution experience with combined therapy.

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.

Adolescent↗

Good outcome of children with acute myeloid leukemia and t(8;21)(q22;q22), even when associated with granulocytic sarcoma: a report from a single institution in Argentina.

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.

Adolescent↗

Childhood acute promyelocytic leukemia: no benefit of all-trans-retinoic acid administered in a short-course schedule.

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.

Adolescent↗

Acute lymphoblastic leukemia presenting as acute hepatic failure in childhood.

We report a 7-year old white girl who was admitted because of acute severe hepatic failure. Her complete blood count revealed pancytopenia and a bone marrow aspiration was consistent with acute lymphoblastic leukemia (ALL). Blasts cells were positive for cytoplasmic CD3 and cell surface T-associated markers. Viral, metabolic, immune and toxic causes for hepatic failure were ruled out. Treatment pre-phase with prednisone was started and liver function tests clearly improved after one-week therapy. However, due to her hepatic insufficiency, daily etoposide was administered orally during 15 days. On day 33 complete remission was achieved and hepatic function was normal, except for an increase in the bilirubin level which normalized on day 72. She received our current treatment for intermediate risk ALL and is still receiving continuation phase therapy, currently, with normal liver function and good tolerance to chemotherapy + 8 months after achieving complete remission.

Anti-Inflammatory Agents↗

Treatment results in childhood acute lymphoblastic leukemia with a modified ALL-BFM'90 protocol: lack of improvement in high-risk group.

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.

Adolescent↗

Acute trilineage leukemia with monosomy of chromosome 7 following an acute promyelocytic leukemia.

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.

Antigens, CD↗

Acute myeloid leukemia as a second malignancy: report of 9 pediatric patients in a single institution in Argentina.

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.

Acute Disease↗

Acute myelogenous leukemia in Down's syndrome: report of a single pediatric institution using a BFM treatment strategy.

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.

Antigens, CD↗

Results of a BFM-based protocol for the treatment of childhood B-non-Hodgkin's lymphoma and B-acute lymphoblastic leukemia in Argentina.

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.

Adolescent↗

Hodgkin disease in children: results of a prospective randomized trial in a single institution in Argentina.

PURPOSE: 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). RESULTS: 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). CONCLUSIONS: 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.

Adolescent↗

Results of treatment with an intensive combination induction regimen containing idarubicin in children with acute myeloblastic leukemia: preliminary report of the Argentine Group for Treatment of Acute Leukemia.

In April 1990, the Argentine Group for Treatment of Acute Leukemia began a multicenter trial for the treatment of previously untreated acute myeloblastic leukemia patients who were under 21 years of age. Initial treatment consisted of an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5 and etoposide on days 6 to 8. A multidrug consolidation phase was subsequently administered and, after a treatment-free interval of 2 to 4 weeks, two 5-day intensification courses with high-dose cytarabine and etoposide were delivered with a 4-week interval between each course. Continuation therapy was started 2 to 4 weeks after the second course, with 6-thioguanine daily and cytarabine daily for 4 days every 4 weeks. Treatment was stopped after 18 months in children in continuous complete remission. A preliminary evaluation of this ongoing study included 36 patients with a mean age of 7.5 years (age range, 5 months to 16 years). The majority of patients had a French-American-British classification of M2 (n = 13) or M4 (n = 8). Complete remission was achieved by 91.7% of patients, while one died from sepsis in bone marrow hypoplasia and two were regarded as treatment failures. At a median follow-up of 12 months (range, 2 to 23 months) there were 12 adverse events: six bone marrow relapses, one bone marrow/skin relapse, and five deaths in complete remission (all deaths occurred during the consolidation phase). During the induction phase most of the patients experienced prolonged myelosuppression, and grade 3 to 4 toxicity (according to the Children's Cancer Group criteria) was frequently seen. Alopecia was universal. However, toxicity was manageable. We conclude that idarubicin in combination with cytarabine and etoposide is a highly effective regimen for induction in children with acute myeloblastic leukemia.

Acute Disease↗

Thyroid dysfunction in Hodgkin's disease.

Radiotherapy to the neck and/or polychemotherapy late effects on the thyroid were investigated in 51 patients (34 males and 17 females) with Hodgkin's disease. Except for two untreated, recently diagnosed patients, all were studied after 1 to 105 months (median, 27.5 months) of completion of polychemotherapy. Age ranged from 6.2 to 36.6 years (median, 13.6 years). Patients were divided according to treatment into four groups: (A) patients treated with CVPP (cyclophosphamide, vinblastine, procarbazine, and prednisone); (B) 22 patients treated with CVPP plus radiotherapy (median radiation dose to the thyroid, 3000 cGy); (C) seven patients with ACOP/BVP (adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin, vinblastine, procarbazine); and (D) seven patients treated with different polychemotherapy protocols, four of whom also received radiotherapy. Elevated basal and/or post-TRH, -TSH levels were found in the following: Group A: two of 12 patients (17%); Group B: 11 of 22 (50%); Group C: four of seven (57%); and Group D: two of seven (28%). Positive antimicrosomal thyroid antibody titers (AM Ab) were found in the following: Group A: three of 12 patients (25%); Group B: six of 21 (28%), Group C: two of seven (28%); and Group D: one of six (17%). Of 46 patients studied, 12 (26%) had positive AM Ab; 37 of 46 patients were younger than 20 years of age, 11 (30%) of whom had positive AM Ab versus 4% in the normal population (P less than 0.001). Two recently diagnosed, untreated patients had either high TSH response to TRH or positive AM Ab. In conclusion, higher frequency of thyroid dysfunction was observed in patients receiving radiotherapy (50% versus 27%). Prevalence of positive AM Ab, apparently unrelated to therapy, was higher in young patients than in the normal population. A predisposition to autoimmune thyroid disease seems to be present in these patients, but it is not possible to discern how lymphoma and thyroiditis are interrelated.

Adolescent↗

Long-term endocrine sequelae after surgery, radiotherapy, and chemotherapy in children with medulloblastoma.

Thirteen children with medulloblastoma, were studied after 2 to 62 months off radiotherapy and chemotherapy with methotrexate and BCNU. Ages at time of study ranged from 2.3 to 15.7 years. Eleven patients, followed for a mean of 22 months, showed a significant decrease of height score, whereas nine patients had deficient growth hormone (GH) response to provocative tests. Clinical pubertal progression was normal in all patients, and three of five girls with advanced pubertal development had menarche. No evidences of gonadotropin disturbances were found in five patients whereas seven had raised basal follicle-stimulating hormone (FSH) level or FSH response to luteinizing hormone-releasing hormone (LH-RH). Abnormalities in thyrotrophin (TSH) secretion were found in 9 of 13 patients. This study shows that poor growth and GH deficiency were frequent in our patients. The high frequency of thyroid disturbances observed point out the need of evaluating thyroid function for adequate replacement therapy. Perhaps modification of adjuvant chemotherapy in the future can diminish drug-induced gonadal damage.

Adolescent↗

Comparison of two consecutive trials for treatment of childhood non-Hodgkin's lymphoma.

Two consecutive trials for the treatment of childhood non-Hodgkin's lymphoma were evaluated, carried out by the same cooperative groups. Group A: From June, 1973 to December, 1975, 50 evaluable patients under 16 years of age participated in a study that included vincristine and prednisone plus surgery and/or radiotherapy as induction. This was followed by 2400 rad of cranial radiotherapy plus 5 doses of intrathecal methotrexate-dexamethasone and anti-leukemia (6-mercaptopurine, methotrexate, cyclophosphamide) or anti-lymphoma (cyclophosphamide, vincristine, procarbazine, and prednisone) maintenance treatment. Group B: From January, 1976 to December, 1980, 55 evaluable patients participated in a consecutive study that added Adriamycin (doxorubicin) and cyclophosphamide to the former induction regimen. Central nervous system (CNS) prevention was performed with 5 doses of intrathecal methotrexate-dexamethasone. Maintenance treatment was the same. Prognostic factors as stage and primary site were comparable in both groups. A total of 33 (66%) of 50 children of Group A and 48 (87%) of 55 children of Group B achieved complete remission (P less than 0.005). Disease-free survival at 60 months was 27% in Group A and 49% in Group B; for Stage I-II, 30% in Group A and 85% in Group B (P less than 0.025); for Stage III-IV 28% in Group A and 36% in Group B (not significant). In Group A, 9.1% and in Group B, 8.3% had primary CNS relapse. Both maintenance schedules had the same relapse rate. It was concluded that: (1) the addition of Adriamycin and cyclophosphamide to vincristine-prednisone in Group B produces a higher rate of complete remission in Stage III-IV, a higher rate of disease-free survival in Stage I-II, and a higher survival rate in all stages; (2) CNS prevention with intrathecal methotrexate-dexamethasone is equally effective as cranial radiation plus intrathecal methotrexate-dexamethasone; and (3) anti-leukemia and anti-lymphoma maintenance are equally effective in the context of this study.

Adolescent↗