Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93.

PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P =.01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P =.007; and 44% v 31%, P =.01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.     

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together /=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.     

Development of treatment and clinical results in childhood acute myeloid leukemia in Slovenia in the period from 1991 to 2010

Background

A review of treatment and survival of children with acute myeloid leukemia (AML) in Slovenia from 1991 to 2010.

Methods

We collected demographic data, information on the time, and course of treatment of patients with AML, which were classified in three risk groups and treated according to standard arm of BFM AML protocols 83, 93, 98, and 04. We assessed the rate of remission, event-free survival and overall survival, the incidence of relapse, the secondary neoplasms, secondary AML, the proportion of patients treated with hematopoietic stem cell transplantation (HSCT) and causes of death. The 2- and 5-year overall survival (5yOS) was estimated according to age group, risk group, the presence of remission, and the time of the treatment.

Results

There were 50 patients, 18 males (36?%) and 32 females (64?%) included in this study. Secondary AML was presented in four patients. Patients treated with HSCT were 18 (36?%), 9 of them in first remission. The 2-year overall survival (2yOS) was 63.7?±?6.8?% and 5-year survival was 55.0?±?7.2?%. Differences in survival between age groups (0–5 years, 6–10 years and more than 10 years) was not significant. All patients in standard risk group lived for more than 2 years, in high-risk group 2yOS was 56.7?±?7.7?% (p?=?0.05). Patients who were in remission before second treatment block had 2yOS 77.8?±?7.4?% and 5yOS 63.8?±?8.8?%, compared to the patients who were not in remission (2yOSand 5yOS 37.5?±?12.1?%, p?=?0.001). The 2yOS in patients treated with HSCT in first remission was 62?%. There were 17 patients (34?%) who had relapse of the disease, 23 (64?%) patients died, 14 (61?%) due to progression of the disease.

Conclusions

The results of treatment of AML in our center are comparable with other European centers. Survival was better in the standard risk group and in patients who were in remission before second treatment block. We observed a trend of improvement in survival in the time observed.     

Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia.

PURPOSE: To assess the efficacy and toxicity of a new treatment program of intensified and shortened cyclical chemotherapy (protocol 8707) in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Previously untreated adults < or = 60 years old with ALL were treated with a four-agent induction chemotherapy regimen. This was followed by cyclical postremission therapy with high-dose cytarabine/etoposide; high-dose methotrexate/6-mercaptopurine; and daunorubicin, vincristine, prednisone, and asparaginase. Maintenance chemotherapy with oral methotrexate and 6-mercaptopurine was continued for 30 months. CNS prophylaxis was given with intrathecal methotrexate in addition to the systemic chemotherapy indicated above. RESULTS: Seventy-eight of 84 patients (93%) achieved complete remission. With a median follow-up of 5.6 years, 5-year event-free survival (EFS) of all remission patients is 52%. Patients with high-risk features including adverse cytogenetics, failure to achieve remission with the first cycle of chemotherapy, and B-precursor disease with WBC counts more than 100,000/microL all relapsed unless taken off study for transplantation. For patients without these high-risk features, 5-year EFS was 60%. Compared with our previous treatment regimen, results appear to be improved for patients with standard-risk B-precursor disease (5-year EFS, 66% v 34%; P =.01). CONCLUSION: Intensified and shortened chemotherapy may improve the outcome for patients with ALL with B-precursor disease lacking high-risk features. Further trials of this regimen are warranted.     

Treatment strategy and results in children treated on three Dutch Childhood Oncology Group acute myeloid leukemia trials.

This report describes the long-term follow-up data of three consecutive Dutch Childhood Oncology Group acute myeloid leukemia (AML) protocols. A total of 303 children were diagnosed with AML, of whom 209 were eligible for this report. The first study was the AML-82 protocol. Results were inferior (5-year probability of overall survival (pOS) 31%) to other available regimes. Study AML-87 was based on the BFM-87 protocol, with prophylactic cranial irradiation in high-risk patients only, and without maintenance therapy. This led to a higher cumulative incidence of relapse than that reported by the Berlin-Frankfurt-Münster (BFM), but survival was similar (5-year pOS 47%), suggesting successful retrieval at relapse. The subsequent study AML-92/94 consisted of a modified BFM-93 protocol, that is, without maintenance therapy and prophylactic cranial irradiation. However, all patients were to be transplanted (auto- or allogeneic), although compliance was poor. Antileukemic efficacy was offset by an increase in the cumulative incidence of nonrelapse mortality, especially in remission patients, and survival did not improve (5-year pOS 44%). Our results demonstrate that outcome in childhood AML is still unsatisfactory, and that further intensification of therapy carries the risk of enhanced toxicity. Our patients are currently included in the MRC AML studies, based on the results of their AML 10 trial.     

Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000.

From 1981 to 2000, a total of 1823 children with acute myeloid leukemia (AML) enrolled on four consecutive Pediatric Oncology Group (POG) clinical trials. POG 8101 demonstrated that the induction rate associated with the 3+7+7 combination of daunorubicin, Ara-C, and 6-thioguanine (DAT) was greater than that associated with an induction regimen used to treat acute lymphoblastic leukemia (82 vs 61%; P=0.02). Designed as a pilot study to determine the feasibility of administration of noncross-resistant drug pairs and later modified to assess the effect of dose intensification of Ara-C during the second induction course, POG 8498 confirmed the high initial rate of response to DAT (84.2%) and showed that dose intensification of Ara-C during the second induction course resulted in a trend toward higher event-free survival (EFS) estimates than did standard-dose DAT (2+5) during the second induction course (5 year EFS estimates, 22 vs 27%; P=0.33). Age <2 years and leukocyte count <100 000/mm3 emerged as significantly good prognostic factors. The most significant observation made in the POG 8498 study was the markedly superior outcome of children with Down's syndrome who were treated on the high-dose Ara-C regimen. POG 8821 compared the efficacy of autologous bone marrow transplantation (BMT) with that of intensive consolidation chemotherapy. Intent-to-treat analysis revealed similar 5-year EFS estimates for the group that underwent autologous BMT (36+/-4.7%) and for the group that received only intensive chemotherapy (35+/-4.5%) (P=0.25). There was a high rate of treatment-related mortality in the autologous transplantation group. The study demonstrated superior results of allogeneic BMT for patients with histocompatible related donors (5-year EFS estimate 63+/-5.4%) and of children with Down's syndrome (5-year EFS estimate, 66+/-8.6%). The POG 9421 AML study evaluated high-dose Ara-C as part of the first induction course and the use of the multidrug resistance modulator cyclosporine. Preliminary results showed that patients receiving both high-dose Ara-C for remission induction and the MDR modulator for consolidation had a superior outcome (5-year EFS estimate, 42+/-8.2%) than did patients receiving other treatment; however, the difference was not statistically significant. These four studies demonstrate the importance of dose intensification of Ara-C in the treatment of childhood AML; cytogenetics as the single most prognostic factor and the unique curability of AML in children with Down's syndrome.     

Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995).

The Dana-Farber Cancer Institute (DFCI) ALL consortium has been conducting clinical trials in childhood acute lymphoblastic leukemia (ALL) since 1981. The treatment backbone has included intensive, multi-agent remission induction, early intensification with weekly, high-dose asparaginase, cranial radiation for the majority of patients, frequent vincristine/ corticosteroid pulses during post-remission therapy, and for high-risk patients, doxorubicin during intensification. Between 1981 and 1995, 1,255 children with newly diagnosed ALL were evaluated on four consecutive protocols: 81-01 (1981-1985), 85-01 (1985-1987), 87-01 (1987-1991) and 91-01 (1991-1995). The 5-year event-free survival (EFS) rates (+/- standard error) for all patients by protocol were as follows: 74 +/- 3% (81-01), 78 +/- 3% (85-01), 77 +/- 2% (87-01) and 83 +/- 2% (91-01). The 5-year EFS rates ranged from 78 to 85% for patients with B-progenitor phenotype retrospectively classified as NCI standard-risk, 63-82% for NCI high-risk B-progenitor patients, and 70-79% for patients with T cell phenotype. Results of randomized studies revealed that neither high-dose methotrexate during induction (protocol 87-01) nor high-dose 6-mercaptopurine during intensification (protocol 91-01) were associated with improvement in EFS compared with standard doses. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.     

Development of treatment and clinical results in childhood acute myeloid leukemia in the Slovak Republic

Background

Acute myeloid leukemia (AML) in children is rare, and it is generally considered to be more resistant to chemotherapy than acute lymphoblastic leukemia. However, because of the gradual intensification of chemotherapy and better supportive care, outcomes have improved considerably over the past 20 years. The management of children with AML in the Slovak Republic was unified and centralized during the second half of the 1990s with the introduction of Berlin-Frankfurt-Munster (BFM) protocols. In 2000, the AML-BFM-1998 protocol was introduced, and data collection became centralized.

Methods and results

Between 2000 and 2009, 73 patients (f?=?38, m?=?35) were treated according to the AML-BFM 1998. Complete remission (CR) was achieved in 89 % of the patients. The 5-year event-free-survival (EFS) and overall survival rates were 47?±?6 % and 52?±?6 %, respectively. The cumulative incidence of relapse was 38 %. The early death (ED) rate and the death rate in CR were both 7 %. The prognosis of children with favorable cytogenetics (standard risk (SR) group) tended to be better than the high-risk group (all other patients; EFS 63 vs. 40 %, p?=?0.15). This tendency was supported by a significantly lower cumulative incidence of relapse in the SR-group (p?=?0.008 by the log-rank test).

Conclusion

Unified treatment protocols and centralized diagnostics improved the management of pediatric AML in the Slovak Republic and increased the overall survival rate to 52 % in the total group and 68 % in children with a favorable cytogenetics. The high relapse rate and treatment-related mortality will be reduced by improving diagnostics, disease control, and the management of treatment-related complications.     

Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report.

The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.     

Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia

BACKGROUND.: It is unknown whether patients with nonleukemic myeloid sarcoma (MS) and those with acute myeloid leukemia (AML) have similar responses to anti-AML treatment. In the current study, the authors addressed this question by matching MS patients with analogous AML patients and comparing their clinical outcomes. METHODS.: Twenty-three consecutive patients with MS and 1720 consecutive patients with AML were identified who presented at The University of Texas M. D. Anderson Cancer Center from 1990 to 2004. All AML patients and 16 MS patients received cytarabine plus idarubicin or fludarabine as induction remission therapy. Treated MS patients and AML patients were matched according to cytogenetics, age, Zubrod performance status, and time of treatment. Event-free survival (EFS) and overall survival (OS) were compared using Kaplan-Meier analyses. RESULTS.: Complete response rates were 69% in patients with MS and 57% in patients with AML (P = .45). The respective 2-year EFS and OS rates were 32% and 18% (P = .08) and 43% and 29% (P = .11). Matches were identified for 14 MS patients who were paired repeatedly with 91 AML patients to produce 94 matches (3 AML patients were matched twice). EFS was longer in 56 MS pair mates, shorter in 26 pair mates, and similar in 12 pair mates (P = .01; Fisher exact test). OS analyses yielded similar results. CONCLUSIONS.: Anti-AML therapy was highly effective in patients with nonleukemic MS. The results from this study emphasize the need to treat patients who have nonleukemic MS with AML-type therapy. Cancer 2008. (c) 2008 American Cancer Society.     

Postremission therapy for acute myeloid leukemia in the first remission

The medical records of 99 patients with acute myeloid leukemia (AML; except AML, M3) in the first remission from 1995 to 2004 were retrospectively reviewed. When they achieved complete remission, at first complete remission (CR1), patients received allogeneic (n = 23), autologous hematopoietic stem cell transplantation (HSCT) (n = 35), or intensive chemotherapy (n = 41) according to prognostic factors and donor availability. There was an advantage in terms of event-free survival (EFS, p = 0.0001) and overall survival (OS, p = 0.0002) with HSCT as compared to those of intensive chemotherapy. However, the EFS and OS were not different between allogeneic HSCT and autologous HSCT. In high-risk patients, the EFS and OS of allogenic or autologous HSCT group were higher compared with those in the intensive chemotherapy group (p < 0.01). However, there was no difference between allogeneic HSCT and autologous HSCT in terms of EFS and OS. In the intermediate- or low-risk group, there was no significant difference in the outcome according to the postremission modalities.     

Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- and long-term effects.

The purpose of this study was to assess the feasibility and efficacy of a treatment regimen for pediatric acute myelogenous leukemia (AML) that uses four rotating drug pairs and adjusts dosages of etoposide and cytarabine to target specific plasma concentrations. Thirty-one girls and 27 boys (median age, 9.7 years) with de novo AML were treated on the protocol. Six cycles of chemotherapy were planned. Cycles 1 to 4 comprised the drug combinations cytarabine plus etoposide, cytarabine plus daunomycin, etoposide plus amsacrine, and etoposide plus azacitidine, respectively. For cycles 5 and 6, the first two combinations were repeated. Dosages were adjusted to achieve plasma concentrations of 1.0 microM +/- 0.1 microM cytarabine and 30 microM +/- 0.3 microM etoposide. Forty-four patients (76%) entered complete remission. Of those, 24 have had relapses; 23 remain alive in first or subsequent remission. The 5-year event-free survival (EFS) estimate was 31.0% +/- 5.9%; the 5-year survival estimate was 41.4% +/- 6.3%. Six patients (10%) died of the toxic effects of therapy. Severe neutropenia occurred in all cycles. Long-term complications of therapy included hepatitis C, cardiac insufficiency, and hearing loss. Adjustment of cytarabine and etoposide dosage was feasible for achieving targeted plasma drug concentrations; however, the potential clinical efficacy of this approach was offset by substantial acute and long-term toxicity.     

European intergroup studies (MMT4-89 and MMT4-91) on childhood metastatic rhabdomyosarcoma: final results and analysis of prognostic factors.

PURPOSE: Final results are presented from two consecutive European studies for patients with metastatic rhabdomyosarcoma (RMS) to identify prognostic variables and determine the value of high-dose chemotherapy (HDCT) in complete remission. PATIENTS AND METHODS: A total of 174 patients aged 3 months to 18 years participated. From 1989 to 1991, patients received four cycles of intensive multiagent chemotherapy. From 1991 to 1995, patients achieving complete remission received consolidation with HDCT. All received local therapy (surgery, radiation therapy) according to response. RESULTS: At a median follow-up of 8 years, 5-year overall survival (OS) and event-free survival (EFS) for the whole group were 24% and 20%, respectively. No statistical difference was found between HDCT and standard chemotherapy (5-year OS, 36% v 27%; EFS 29% v 23%). Univariate analysis identified primary tumor in parameningeal, extremity, or other sites; age younger than 1 year and older than 10 years; bone or bone marrow metastases; multiple metastases; and multiple sites of metastases as unfavorable prognostic factors for OS and EFS. Multivariate analysis identified unfavorable site, bone or bone marrow involvement, and unfavorable age as independently unfavorable factors. Two subgroups were identified. Those with fewer than two unfavorable factors had 5-year EFS and OS of 40% and 47%, respectively. Patients with > or = two unfavorable factors had 5-year EFS and OS of 7.5% and 9%, respectively. CONCLUSION: A minority of patients with metastatic RMS have better survival than overall results for this population suggest. Those in the highest risk group have such poor survival that they are candidates for first-line novel therapies. There is no evidence that consolidation with HDCT improves outcome.     

Outcomes of Adolescents and Young Adults With Acute Myeloid Leukemia Treated in a Single Latin American Center

Introduction

The outcomes for adolescents and young adults (AYAs) with acute myeloid leukemia (AML) have been poorly characterized in Hispanics in low- to middle-income countries. The results are influenced by biologic and socioeconomic factors. The clinical paths for AYA patients with AML are reported.

Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy

570 patients with osteosarcoma of the extremities were treated with five different protocols of neoadjuvant chemotherapy at Rizzoli Institute between 1983 and 1995. Surgery consisted of limb salvage in 83% rotation plasty in 5% and amputation in 12%. The 5-year event-free survival (EFS) was 60% which varied according to the protocol followed, ranging from 47.6% to 66.4%. 234 patients relapsed. The pattern of relapse was analysed. The mean relapse time was 23.8 months (range: 2-96). The first site of systemic relapse was the lung in 88% (32% of these had less than three pulmonary metastases and 68% three or more), bone in 9%, lung and bone in 2% and other sites in 3%. The relapse time and the number of pulmonary metastases were strictly correlated with the efficacy of the protocol of chemotherapy used. Patients treated with the three protocols that gave a 5-year EFS of more than 60% relapsed later and had fewer pulmonary lesions than patients treated with the two protocols that gave a 5-year EFS of 47.6% and 52.5%. The rate of local recurrence was relatively low (6%). This was not correlated with the protocol or the type of surgery used: limb salvage (6.4%), rotation plasty or amputation (4.1%). However, the rate of local recurrence was very high (21.9%) in the few patients (7%) that had less than wide surgical margins. We conclude that for patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy: (a) the pattern of systemic relapse changes according to the efficacy of the protocol of chemotherapy used. This should be always considered when evaluating the preliminary results of new studies as well as in defining the time of follow-up; (b) limb salvage procedures are safe and do not jeopardise the outcome of the patient, provided that wide surgical margins are achieved.     

Retrospective Analysis of Childhood Hepatoblastoma in a Single Centre in China

AimsTo investigate the protocol efficacy and prognostic factors for paediatric hepatoblastoma in a multidisciplinary model in our centre.Materials and methodsConsecutive hepatoblastoma patients (<18 years old) treated at Shanghai Children's Medical Center in China from August 2011 to October 2017 were analysed retrospectively for clinical features, chemotherapy courses, surgical treatment and outcomes.ResultsOne hundred and four cases of paediatric hepatoblastoma (64 males, 40 females; median age at diagnosis 1.64 years) had a median follow-up of 30.68 months (range 8.3–73.3 months). First complete remission was achieved in 95 cases, 85 of which achieved continuous complete remission. Another three cases were lost to follow-up after a median of 24.73 months in complete remission. Seven cases relapsed later, with two achieving a second complete remission and four deaths. Nine cases did not achieve complete remission and five of them died. In general, the 5-year overall survival rate and 5-year event-free survival (EFS) rate were 86.3 ± 5.0% and 81.8 ± 4.3%, respectively. Thirty-two cases were classified as standard risk and 72 as high risk with 5-year EFS of 96.8 ± 3.2% and 75.7 ± 5.7% (P = 0.029) and 5-year overall survival of 100% and 80.5 ± 7.0%, respectively. The mean platelet count (P = 0.0036), lactate dehydrogenase (P = 0.0443) and ferritin level (P = 0.0006) at diagnosis were much higher in the high-risk group than in the standard-risk group. Univariate analysis showed that patients <5 years of age (P = 0.018), with higher α-fetoprotein (AFP) level (>100 ng/ml, P = 0.008), without metastases at diagnosis (P = 0.001) and postoperative AFP recovery after no more than three chemocycles (P = 0.014) had better overall survival. In addition, the above factors, except metastases at diagnosis and risk group, were associated with prognosis in the multivariate analysis.ConclusionsThe result of this protocol had similar overall survival and EFS rates compared with those in developed countries. Normal postoperative AFP levels after three chemocycles has prognostic value.     

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.     

Excellent Survival Outcomes of Pediatric Patients With Acute Myeloid Leukemia Treated With the MASPORE 2006 Protocol

PurposeTo determine the prognostic factors in pediatric patients with acute myeloid leukemia (AML) and to assess whether their outcomes have improved over time.Patients and MethodsSixty-two patients with AML excluding acute promyelocytic leukemia were retrospectively analyzed. Patients in the earlier cohort (n = 36) were treated on the Medical Research Council (MRC) AML12 protocol, whereas those in the recent cohort (n = 26) were treated on the Malaysia–Singapore AML protocol (MASPORE 2006), which differed in terms of risk group stratification, cumulative anthracycline dose, and timing of hematopoietic stem-cell transplantation for high-risk patients.ResultsSignificant improvements in 10-year overall survival and event-free survival were observed in patients treated with the recent MASPORE 2006 protocol compared to the earlier MRC AML12 protocol (overall survival: 88.0% ± 6.5% vs 50.1% ± 8.6%, P = .002; event-free survival: 72.1% ± 9.0 vs 50.1% ± 8.6%, P = .045). In univariate analysis, patients in the recent cohort had significantly lower intensive care unit admission rate (11.5% vs 47.2%, P = .005) and numerically lower relapse rate (26.9% vs 50.0%, P = .068) compared to the earlier cohort. Multivariate analysis showed that treatment protocol was the only independent predictive factor for overall survival (hazard ratio = 0.21; 95% confidence interval, 0.06-0.73, P = .014).ConclusionOutcomes of pediatric AML patients have improved over time. The more recent MASPORE 2006 protocol led to significant improvement in long-term survival rates and reduction in intensive care unit admission rate.     

Randomized controlled study of chemoimmunotherapy of acute myelogenous leukemia (AML) in adults with Nocardia rubra cell-wall skeleton and irradiated allogeneic AML cells

The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5-year relapse-free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.     

Postremission chemotherapy for adults with acute myelogenous leukemia: improved survival with high-dose cytarabine and daunorubicin consolidation treatment.

Results of postremission chemotherapy for adults with acute myelogenous leukemia (AML) were assessed in two sequential prospective studies involving similar induction therapy and two courses of intensive consolidation treatment. Fifty-six patients achieving remission on the acute leukemia protocol (ALP3) study received high-dose cytarabine and daunorubicin as course one and standard-dose cytarabine and daunorubicin as course two. Results are compared with forty-six patients achieving remission on the ALP2 study who received azacitidine and doxorubicin as consolidation course one and standard-dose cytarabine, daunorubicin, and thioguanine as course two. The ALP3 regimen resulted in a significantly improved 5-year disease-free survival of 32% +/- 19% versus 20% +/- 11% for the ALP2 study (P = .03). Survival from remission was also improved, 40% +/- 14% versus 24% +/- 12% (P less than .01). Favorable prognostic factors for disease-free survival included receiving the ALP3 treatment regimen, absence of a prior preleukemic syndrome, and female sex. These factors and younger patient age were significant for survival following first chemotherapy and survival after achieving remission. Six of 34 patients who relapsed after receiving the ALP3 regimen successfully achieved prolonged second remissions with high-dose cytarabine-based chemotherapy and/or allogeneic bone marrow transplantation (BMT). Overall survival for adults less than or equal to 45 years of age was 58% +/- 19% with the ALP3 postremission chemotherapy regimen, comparable to most studies of BMT for AML in first remission. Actuarial 5-year survival for ALP3 patients greater than 60 years of age was 18% +/- 20% with no improvement compared with ALP2.