Localized bone marrow relapse in acute lymphoblastic leukemia

Localized bone marrow relapse is rare in acute lymphoblastic leukemia. Discordant bone marrow specimens were found in an 11-year-old asymptomatic girl who had been in remission for six years and off chemotherapy for 2 1/2 years. One bone marrow sample showed marked leukemic infiltration, whereas marrow from another site was normal. Three months later, with normal peripheral blood counts, she developed severe back pain and x-ray evidence of vertebral collapse and periosteal changes in the public bone. At that time three of the four areas of bone marrow sampled showed leukemic involvement. Reinduction therapy was begun, and she is now in remission on maintenance chemotherapy. At this time, it is unclear whether routine performance of marrow aspirations and biopsies from multiple sites, in periodic follow-up examinations of patients with acute leukemia would allow earlier detection of relapse frequently enough to justify the procedure. The issue of localized bone marrow involvement, if more common than previously reported, should be addressed at the time a decision is being made to discontinue therapy.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.     

Failure of early intensive chemotherapy to improve prognosis in childhood acute lymphocytic leukemia

The ability of intensive therapy, early in remission, to improve prognosis in childhood acute lymphocytic leukemia was tested in a randomized study. The intensive treatment included cyclophosphamide (200 mg/m² IV weekly × 4) and Adriamycin (40 mg/m² IV weeks 1 and 3). These drugs were not utilized during the induction or continuation phases of therapy. Treatment groups were similar with respect to patient age, sex, initial white cell count, and leukemic cell immunologic phenotype. Sixteen of 28 children who received the intensive phase of treatment relapsed, and one died in remission (pneumocystis pneumonia); 14/26 children who did not receive the intensive phase of treatment relapsed, and one died in remission (malignant histiocytosis). Times and sites of relapse were similar in both groups. Pneumocystis pneumonia (three cases) and herpes zoster (two cases) occurred only in children who received the intensive phase of treatment. In this study and in previously published reports, an early intensive phase of therapy did not improve prognosis in children with acute lymphocytic leukemia who also received three-drug induction therapy, central nervous system prophylaxis, and continuation therapy with two or more agents.     

以高钙血症和骨质改变为首发表现的儿童急性淋巴细胞白血病1 例报告

目的探讨以骨质改变和高钙血症为首发表现的儿童急性淋巴细胞白血病(ALL)的临床特点及诊治。方法回顾分析1例以骨质改变和高钙血症为首发表现的儿童B细胞ALL的临床资料。结果患儿,男性,6岁5个月,以腹痛起病,初期检查发现骨质改变及高钙血症,后确诊ALL。采用CCLG-ALL-2015方案化疗,同时加用伊马替尼口服,目前已获得缓解。结论高钙血症和骨质改变可以是B细胞ALL首发表现。     

诱导化疗早期骨髓检查判断急性淋巴细胞白血病高危因素的价值

为分析小儿急性淋巴细胞白血病诱导化疗早期骨髓象与预后的关系,对１０８例初治小儿急性淋巴细胞白血病进行ＭＩＣ分型并随访,于诱导化疗第８天行骨髓检查,以骨髓幼稚细胞〉０．２０为Ａ组,骨髓幼稚细胞〉０．２０为Ｂ缚结果：（１）Ａ组生存率明显高于Ｂ组（分别为８４．２％和１８％,Ｐ〈０．０５）。（２）Ａ组中临床高危型比例明显低于Ｂ组（分别为７２％和６６％,Ｐ〈０．０５）。（３）临床普危型的病例中Ａ组复发率明显     

Acute nonlymphoblastic leukemia in children treated for acute lymphoblastic leukemia with an intensive regimen including teniposide

Some cases of conversion from acute lymphoblastic leukemia (ALL) to acute nonlymphoblastic leukemia (ANLL) at relapse have been reported recently. We report three cases initially diagnosed as having ALL and showing morphological, cytochemical, and immunophenotypic features of ANLL at relapse (lineage switch). Conversion was observed among 14 patients who developed bone marrow relapse while undergoing intensive treatment with our ALL protocol, which includes teniposide, and that had been administered to 62 patients. The three cases converted at first relapse, with a mean time of 20 months (13–29 months). Clinical and immunologic characteristics of T-cell leukemia were present in one patient. Changes documented in cytogenetic studies are discussed. The underlying mechanisms for the lineage switch remain unclear as does its relation with mixed lineage leukemias, but we believe that drugs employed in our therapy protocol could have had an influence on this conversion.     

ALL-2005方案对儿童急性淋巴细胞白血病髓外白血病防治效果分析

目的总结ALL-2005方案对急性淋巴细胞白血病(ALL)患儿髓外白血病,包括中枢神经系统白血病(CNSL)及睾丸白血病(TL)的防治效果。方法 2005年5月—2008年5月共218例ALL患儿,采用ALL-2005方案进行治疗,总结其临床及治疗情况。结果 218例ALL患儿中,5例初诊时伴CNSL,1例于诱导治疗期间发生CNSL,4例于维持治疗期间发生CNSL;1例初诊时伴TL发生,4例维持治疗期间发生TL。经治疗,2例CNSL患儿骨髓复发,其余8例均缓解至今;TL患儿1例骨髓复发,1例放弃治疗,3例缓解至今。结论 ALL-2005方案疗效良好,有利于提高患儿长期生存质量。[临床儿科杂志,2012,30(5):412-414]     

替尼泊苷在儿童急性淋巴细胞白血病中的应用

替尼泊苷(VM26)为半合成的鬼臼毒素的糖基衍生物，在儿童多用于治疗急性淋巴细胞白血病(ALL)。为探讨ALL在巩固、早期强化及维持加强化疗阶段应用VM26 Ara—C前后血常规变化规律，对155例次ALL患儿应用VM26 Ara-C治疗前、后血常规变化情况进行统计分析。结果：用药后白细胞、血小板于第11—13天降到最低值，于3周恢复正常。注射G—CSF对白细胞的恢复有作用。提示VM26对骨髓的抑制作用是其主要副作用，为保证化疗的顺利、安全进行，临床医师应了解其对骨髓的影响程度，从而有效地发挥其抗癌作用。减少毒副作用的有效措施即为给药剂量的个体化。     

Outcome after first relapse in children with acute lymphoblastic leukemia: a report based on the Dutch Childhood Oncology Group (DCOG) relapse all 98 protocol

Background

We report on the treatment of children and adolescents with acute lymphoblastic leukemia (ALL) in first relapse. The protocol focused on: (1) Intensive chemotherapy preceding allogeneic stem cell transplantation (SCT) in early bone marrow relapse; (2) Rotational chemotherapy in late relapse, without donor; (3) Postponement of cerebro‐spinal irradiation in late isolated CNS relapse; and (4) Treatment in very late bone marrow relapse with chemotherapy only.

Methods

From January 1999 until July 2006 all 158 Dutch pediatric patients with ALL in first relapse were recorded. Ninety‐nine patients were eligible; 54 patients with early and 45 with late relapse. Eighteen patients had an isolated extra‐medullary relapse; 69 patients had bone marrow involvement only.

Results

Five‐years EFS rates for early and late relapses were 12% and 35%, respectively. For early relapses 5 years EFSs were 25% for patients transplanted; 0% for non‐transplanted patients. For late relapses 5 years EFS was 64% for patients treated with chemotherapy only, and 16% for transplanted patients. For very late relapses EFS was 58%.

Conclusions

Our data suggest the superiority of SCT for early relapse patients. For late relapses a better outcome is achieved with chemotherapy only using the rotational chemotherapy scheme. The most important factor for survival was interval between first CR and occurrence of the first relapse. Pediatr Blood Cancer 2011; 57: 210–216. © 2011 Wiley‐Liss, Inc.

     

Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia

In a retrospective review which covered the whole Dutch childhood population of approximately 3 million children we studied the prognosis in 164 children with acute lymphoblastic leukemia (ALL) who were initially treated between 1973 and 1983, and who had an isolated bone marrow relapse occurring as first relapse. Until their first relapse, the patients were initially treated according to standard protocols, while treatment for relapse was heterogeneous, and not intensive. Second complete remission (CR) was attained by 78% of the patients. The median duration of second CR was 9 months, the median survival 13 months. Multivariate analysis showed that the duration of the first CR was the most significant variable with regard to prognosis. None of the patients who developed their bone marrow relapse during initial treatment, i.e., within 24 months from diagnosis, survived. Among the 73 patients who relapsed after cessation of the initial treatment there were 19 long-term disease-free survivors, 14 of whom had not developed subsequent relapses after 48+-125+ months. From this study we conclude that treatment in children with first bone marrow relapse has to be intensified.     

Toxicity and outcome of children with treatment related acute myeloid leukemia

Background

The aim of this study was to evaluate the clinical course and outcome of children with treatment related acute myeloid leukemia (tAML) and compare them to children with primary AML (pAML).

Procedure

We retrospectively reviewed the demographic, treatment, toxicity, and outcome data of children with tAML and treatment related myelodysplastic syndrome (tMDS), treated at our institution between 1975 and 2005. We compared these parameters with matched controlled children with pAML. Finally we compared overall survival (OS) for tAML with all pAML children treated at the study era in our institution.

Results

Twenty‐one patients with tAML (n = 19) and tMDS (n = 2) were identified. Three years event‐free survival (EFS) and OS were both 14 ± 8%. Compared to pAML patients, tAML had a higher rate of adverse cytogenetics (P < 0.008) and inferior OS (P = 0.027) but no significant difference in treatment toxicity or death. All survivors were treated with allogeneic hematopoietic stem cell transplantation (HSCT).

Conclusions

In this population based report of pediatric tAML, outcome was poor and was related to a higher probability of poor cytogenetic features rather than excessive toxicities or inability to deliver therapy. HSCT should be considered for patients with tAML. These preliminary findings should set the stage for prospective cooperative studies. Pediatr Blood Cancer 2008;50:17–23. © 2007 Wiley‐Liss, Inc.     

儿童急性淋巴细胞白血病复发与基因突变相关性

急性淋巴细胞白血病是儿童恶性肿瘤中最常见的类型,急性淋巴细胞白血病复发仍然是治疗的难题.随着近几年关于儿童急性淋巴细胞白血病复发机制的研究逐渐深入,越来越多的基因异常已经被证实与儿童急性淋巴细胞白血病复发相关,包括IKZF1缺失、PRED1缺失、JAK突变、CREBBP突变、CEBPE突变、ARID5B突变等.该文重点综述以上基因突变对儿童急性淋巴细胞白血病复发的影响.     

MicroRNA expression and activity in pediatric acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is the most common type of pediatric neoplasia. Highly heterogeneous, ALL includes several genetic subtypes with varying clinical outcome. Although, some features are well established as prognostic predictors, the details of the molecular mechanisms underlying different phenotypes are only beginning to emerge. Recently, microRNAs (miRNAs) have been shown to influence a range of physiological processes and, consequently, alterations in their expression and functions have been associated with the development of many cancers, including leukemia. This article aims to review the current state of knowledge of the role of miRNAs on the biology of childhood ALL, also including relevant findings from the adult leukemia literature.     

Asparagine depletion after pegylated E. coli asparaginase treatment and induction outcome in children with acute lymphoblastic leukemia in first bone marrow relapse: a Children's Oncology Group study (CCG-1941)

PURPOSE: Re-induction outcomes vary for children with acute lymphoblastic leukemia (ALL) and marrow relapse. We explored possible relationships among asparaginase (ASNase) activity levels, asparagine (ASN) depletion, anti-ASNase antibody titers, and response to re-induction therapy in children and adolescents with ALL and an 'early' first marrow relapse. PATIENTS AND METHODS: After appropriate informed consent, we enrolled children and adolescents 1-21 years old with ALL and first marrow relapse within 12 months of completion of primary therapy. Induction therapy included intramuscular pegylated ASNase on Days 2 and 16. We assessed ASNase activity, anti-ASNase antibody titers against native and pegylated (E. coli) ASNase, and amino acid levels of asparagine (ASN) and glutamine (GLN) on Days 0, 14, and 35 of re-induction. RESULTS: Ninety-three patients were at least partially assessable. Among 21 patients with M1 marrow status at Day 35, the median Day 14 ASN level was <1 microM. This is significantly lower than the median Day 14 ASN level of 4 microM in the group of patients with M3 marrow at Day 35. Neither Day 0 nor Day 35 antibody titers predicted ASNase enzymatic activity level on Day 14. Surprisingly, Day 14 ASNase activity did not predict serum ASN level on Day 14. However, Day 0 and Day 35 anti-native ASNase antibody titers, and Day 0 anti-PEG ASNase antibody titers correlated positively with Day 14 serum ASN levels as one might expect from neutralizing antibody. Day 35 anti-PEG ASNase antibody titers did not. CONCLUSIONS: Patients with greater ASN depletion were more likely to achieve second remission in the context of six-drug therapy.     

儿童急性淋巴细胞白血病化疗后免疫系统重建的研究

目的 观察急性淋巴细胞白血病(ALL)儿童在化疗结束后淋巴细胞亚群和免疫球蛋白的变化,了解化疗后免疫系统的恢复过程.方法 采用流式细胞仪分析76例ALL治疗后停药患儿的外周血淋巴细胞亚群,应用单向琼脂扩散法测定其中64例患儿血清IgA、IgG、IgM的浓度.结果 CD3 HLA-DR 细胞、CD4 CD45RO-CD45RA-细胞百分率在停药后0～12个月组高于对照组(P<0.05),CD3 CD4-CD8 、CD8 CD28-细胞百分率在停药后0～12个月、12～24个月、24～48个月组均高于对照组,CD3 CD8-CD4 、CD4 CD29-、CD4 D45RO-CD45RA 细胞的百分率、CD4/CD8比值、CD45RA/CD45RO比值在停药各个阶段与对照组相比明显降低(P<0.05).CD19 CD5 细胞的百分率在停药后0～12个月、12～24个月组高于对照组,IgG浓度停药0～12个月低于参考值(P<0.05).结论 化疗结束后,患儿的免疫系统恢复需要较长的时间.NK细胞在停药时即正常.B细胞在停药2年后已经基本恢复,T淋巴细胞的恢复最慢.     

Continued complete remission without systemic therapy for isolated testicular relapse after bone marrow transplantation in a boy with acute lymphoblastic leukemia

Abstract:  ITR after BMT in cases of acute lymphoblastic leukemia is relatively rare. Treatment for ITR after BMT generally consists of a combination of local irradiation, orchiectomy, and systemic chemotherapy. However, the effectiveness of these modalities has not been established. Both irradiation and systemic chemotherapy including a second transplantation would result in additional toxicity. In this report we describe a boy with ITR 91 months after BMT who has remained in complete remission more than two yr after a unilateral orchiectomy. We did not treat this patient with systemic chemotherapy, as his ITR developed very late. Our experience suggests that orchiectomy alone is a reasonable option for very late ITR after BMT.     

Novel multiagent chemotherapy for bone marrow relapse of pediatric acute lymphoblastic leukemia

BACKGROUND: Despite improvements in the treatment of pediatric acute lymphoblastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited institution study sought to improve event-free survival (EFS) by intensification of chemotherapy. PROCEDURE: Twenty-one patients with either an isolated marrow (n = 16) or a combined marrow and central nervous system relapse (n = 5) received treatment according to Children's Hospital of Philadelphia protocol CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Induction and reinduction therapy consisted of idarubicin, vincristine, dexamethasone, asparaginase, and triple intrathecal chemotherapy. Consolidation and reconsolidation therapy employed high-dose cytarabine, etoposide, and asparaginase given in a sequential manner. Maintenance therapy included courses of high- or low-dose cytarabine followed by sequential etoposide and asparaginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from the start of interim maintenance in the 16 patients who did not receive a bone marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternative donor BMT. RESULTS: The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the actuarial EFS based on intent to treat is 75%. There were three toxic deaths in patients in CR and two deaths from relapse. CONCLUSIONS: This regimen is toxic but effective and deserves study in a larger setting.