Late Relapses in Acute Lymphoblastic Leukemia

Two children presented with relapsed acute lymphoblastic leukemia 6 years and 8 years after cessation of maintenance treatment. Relapses this length of time off treatment are unusual, with only 7 previously reported cases. It is often unclear whether the relapse is of the original disease or a second leukemia, and our results in both cases suggest relapse of their primary disease.     

Extramedullary Relapse in Childhood Leukemia

As long-term survival of children with leukemia is increasing, the prophylaxis of extramedullary leukemia has become a more important part of treatment. We studied the pattern of occurrence of extramedullary leukemia in a retrospective review. This review included a total of 2317 childhood leukemia patients aged 15 years or less who had been treated at 38 institutes in Japan between 1976 and 1985. Extramedullary leukemia developed in 386 of 1,724 ALL patients (22.4%) and 63 of 544 patients with ANLL (163%). Among the ALL patients, CNS-L was the most common form and was observed in 315 cases (81.6%), followed by testicular leukemia in 89 (23.0%). In the case of ANLL, the most common form of extramedullary leukemia was CNS-L (45 cases, 71.4%), followed by cutaneous leukemia in 10 cases (15.9%). In addition, leukemia of the lymph nodes, ovaries, bones, kidneys and eyes was observed in 7, 5, 5, 4 and 4 cases, respectively. The survival rate of ALL patients with CNS-L was 40.1% for isolated relapse and 2.7% for bone marrow relapse, and no more deaths occurred after 6 years from relapse. The survival rate of patients with testicular leukemia was 40.1% for isolated relapse and 5.9% for complicating bone marrow relapse, and no deaths occurred after 7 years from relapse. Cutaneous leukemia tended to occur late in older children with ALL and early in infants with ANLL, and all these patients died. Infiltration into the kidney was observed in 4 patients, all of whom died. More than 75% of patients died after isolated relapse of leukemia of the bones, ovaries, lymph nodes and eyes. Prophylactic extramedullary leukemia therapy, of CNS-L in particular, has played an important role in the treatment of childhood leukemia. Careful development of more effective therapy and close observation of late effects are required when monitoring affected children who are still growing.     

TEN CASES OF SO-CALLED LONG SURVIVAL IN CHlLDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Abstract. Armata, J. Cyklis, R. and Wyszkowski, J. (Institute of Paediatrics, Medical Academy in Cracow, Cracow, Poland). Ten cases of so-called long survival in children with acute lymphoblastic leukemia. Acta Paediatr Scand 63: 369, 1974.–Ten cases of acute lymphoblastic leukemia are presented, in children all of whom survived more than 4 years. WBC and blast cell counts were registrered at low levels at the onset of the disease and at subsequent bone marrow relapses. Extramedullary leukemia occurred after 2 years (average) in bone marrow remission, which did not predict early bone marrow relapse. From 1962 to 1970 three treatment regimens for acute leukemia were compared; the best results depended on the intensity of treatment during the first remission.     

Non Hodgkin’s lymphoma seven years following remission of acute lymphoblastic leukemia

The authors describe a case of extramedullary relapse in lymph node presenting as lymphoblastic lymphoma seven years following remission of acute lymphoblastic leukemia. To the best of our knowledge, this is the first reported case of an isolated lymph node relapse with hematopoietic remission of leukemia. We have discussed cases of large cell lymphoma and other unusual areas of extramedullary relapse complicating acute lymphoblastic leukemia in hematopoietic remission.     

儿童急性髓系白血病微小残留病检测技术的应用进展

近年来,虽然儿童急性髓系白血病(acute myeloid leukemia,AML)的治疗效果有了很大改善,但其复发仍然是影响预后的主要因素.大量研究表明微小残留病(minimal residual disease,MRD)的水平不仅与AML复发密切相关,而且对于判断其预后、指导个体化治疗同样具有重要意义.寻找特异性高、灵敏度高、简便、适用的检测方法一直是MRD研究的热点之一,该文将对AML的MRD检测技术最新的应用进展进行综述.     

AML-XH-99方案治疗婴幼儿急性髓系白血病临床总结

目的探讨婴幼儿急性髓系白血病(AML)的临床特征及采用AML-XH-99方案的疗效。方法 1998年5月至2009年4月诊断的0～3岁AML(除外M3)26例,采用AML-XH-99方案化疗。应用SPSS13.0软件统计,采用Kaplan-Meier生存分析法进行无事件生存(EFS)分析。结果 26例患儿中M5居首(61.54%),其次为M2(26.92%)。年龄>12个月22例,<12个月4例,7例(26.92%)起病时外周血白细胞>50×109/L,5例(19.23%)染色体核型异常,5例(19.23%)在诱导治疗结束后48 h的骨髓涂片中幼稚细胞比例>15%。24例(92.31%)第1疗程获完全缓解(CR),总缓解率为96.15%。5例(19.23%)骨髓复发,中位复发时间为完全持续缓解(CCR)15.8个月。3例在强化疗后接受异体造血干细胞移植。26例中1例失访,7例死亡(5例死于疾病复发,2例死于治疗相关并发症)。中位CCR时间为4.08年,7年EFS为60.72%。结论 AML-XH-99方案治疗婴幼儿急性髓系白血病缓解率高,预后良好。     

Isolated testicular leukemia following bone marrow transplant for acute lymphocytic leukemia. The need for pretransplant testicular biopsies

Bone marrow transplantation has become an accepted mode of treatment for children with acute myelocytic leukemia in their first remission and acute lymphocytic leukemia after their first bone marrow relapse. Two-year survival rates of 50% can be achieved in patients undergoing transplant during remission, in contrast to a 2-year survival of 15% in those undergoing transplant while still in marrow relapse. Recurrence of bone marrow leukemia relapse is a significant cause of marrow transplant failure. Overt or occult testicular relapse occurs in 10-15% of males with acute lymphocytic leukemia receiving or having completed standard therapy regimens for control of their disease and frequently leads to a subsequent bone marrow relapse. This paper describes a child with acute lymphocytic leukemia who received a successful marrow transplant following bone marrow relapse and developed testicular leukemia relapse approximately 20 months after transplant. The experience with this child suggests that bilateral testicular biopsies should be a mandatory part of the routine evaluation to screen for residual leukemia before bone marrow transplantation.     

Marrow transplant experience in children with acute lymphoblastic leukemia: an analysis of factors associated with survival, relapse, and graft-versus-host disease

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.     

Acute lymphoblastic leukemia in a girl with Wilson's disease

Wilson's disease (WD) is an autosomal recessive defect in cellular copper transportation. Although acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy, only two cases of ALL associated with WD have been reported to date. One patient died of relapse and infection, and the other died of neutropenic sepsis during the treatment. We here describe the case of a 10‐year‐old girl with WD and ALL. Adverse events of chemotherapy, including liver toxicity and severe myelosuppression, necessitated adjustments in the chemotherapy doses. After completion of the treatment, the patient has remained in remission from ALL without progression of liver damage for 2 years. Severe treatment‐related toxicity should be considered in chemotherapy for patients with WD.     

Isolated testicular and bone relapse in children with acute myeloblastic leukemia and chronic graft versus host disease after allogeneic BMT

Isolated extramedullary relapse after allogeneic bone marrow transplantation (BMT) for acute myeloblastic leukemia (AML) is very unusual, particularly in patients with graft versus host disease (GVHD) known to be associated with decreased incidence of leukemic relapses. However, these rare occasions have been suggested to result from the escape of leukemic cells at the immune-privileged sites. Here we report two unusual post-transplant cases with AML: the first developed testicular relapse during the treatment of chronic GVHD (cGVHD) and bronchiolitis obliterans and the second relapsed as granulocytic sarcoma in the proximal tibia two years after BMT.     

去甲氧柔红霉素联合方案治疗难治性急性淋巴细胞白血病的远期疗效

目的探讨应用去甲氧柔红霉素（ＩＤ）为主的联合化疗方案治疗难治性儿童急性淋巴细胞白血病（ＡＬＬ）的远期疗效及其临床应用价值。方法初治诱导缓解方案用ＶＩＬＰ（长春新碱、去甲氧柔红霉素、左旋门冬酰胺酶、泼尼松）。完全缓解（ＣＲ）后作巩固治疗及庇护所治疗，然后再用ＶＩＬＰ作早期强化治疗。复发者诱导治疗用ＩＡ（去甲氧柔红霉素、阿糖胞苷）方案。ＣＲ后巩固和早期强化治疗用初治者同样方案。结果１０例初治患儿９例获ＣＲ，７例复治患儿５例获ＣＲ，总ＣＲ率为８２％（１４／１７）。ＣＲ的１４例中持续ＣＲ（ＣＣＲ）＞３年者４例，＞２年者４例，＞１年者１例。结论用去甲氧柔红霉素为主的联合方案是治疗难治性儿童ＡＬＬ有效的方法，对初治患儿作为一线药物其远期疗效会更好。     

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.     

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.     

Comparison of Autologous and Allogeneic Bone Marrow Transplantation in Children with Acute Leukemia

Thirty-one patients with acute non-lymphocytic leukemia (18 patients) or with high-risk refractory acute lymphocytic leukemia (13 patients) underwent bone marrow transplantation between March 1980 and March 1990. The high-dose conditioning regimen employed included cyclophosphamide followed by fractionated total body irradiation (12 GY). Fourteen patients who had an HLA-identical sibling donor received allogeneic bone marrow transplantation (ailo-BMT); the other 17 patients received autologous bone marrow transplantation (auto-BMT) purged with 4-hydroperoxycyclophosphamide (4HC). Four of the 14 allo-graft recipients died of leukemic relapse and 2 others died of graft-versus-host disease. Three of the 17 auto-graft recipients died of relapse and 1 suffered relapse in the testes. The actuarial risk of relapse was 29% for the allo-BMT patients and 24% for the auto-BMT patients (P<0.05). The event-free survival rate at five years was 57% and 74% respectively (P<0.05). Although there was no difference between them, a trend toward a higher survival rate and a lower mortality and morbidity was observed in the auto-BMT group. These results suggest that autologous bone marrow transplantation purged with 4HC is an effective and useful treatment for children with acute non-lymphocytic and lymphocytic leukemia who have no HLA-identical donor.     

Serial determination of serum ferritin in children with acute lymphoblastic leukemia. Evaluation of its usefulness as a prognostic index.

Thirty children with acute lymphoblastic leukemia were monitored with serial serum ferritin determinations for up to 17 months. In children with acute lymphoblastic leukemia before initiation of therapy, or in relapse, the mean serum ferritin concentration was 636 microgram/l. In children who went into primary remission. the mean serum ferritin concentration fell from 265 microgram/l prior to start of treatment, to 161 microgram/l after 3 months of treatment. Five patients relapsed. Their serum ferritin levels prior to the relapses ranged from 7 to 135 microgram/l. At the time of relapse a further increase in serum ferritin was found in only 2 of the children. Thus, whereas high serum ferritin levels may signal disease activity in acute lymphoblastic leukemia, a normal serum ferritin level does not exlude disease activity or impending relapse.     

SERIAL DETERMINATIONS OF SERUM FERRITIN IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA Evaluation of its Usefulness as a Prognostic Index

Abstract. Thirty children with acute lymphoblastic leukemia were monitored with serial serum ferritin determinations for up to 17 months. In children with acute lymphoblastic leukemia before initiation of therapy, or in relapse, the mean serum ferritin concentration was 636 μg/l. In children who went into primary remission, the mean serum ferritin concentration fell from 265 μg/l prior to start of treatment, to 161 μg/l after 3 months of treatment. Five patients relapsed. Their serum ferritin levels prior to the relapses ranged from 7 to 135 μg/l. At the time of relapse a further increase in serum ferritin was found in only 2 of the children. Thus, whereas high serum ferritin levels may signal disease activity in acute lymphoblastic leukemia, a normal serum ferritin level does not exclude disease activity or impending relapse.     

Allogeneic bone marrow transplantation in acute lymphoblastic leukemia of children. Analysis of prognostic factors. GEGMO (Bone Marrow Study Group) study

Sixty-five children with acute lymphoblastic leukemia (ALL) underwent allogenic bone marrow transplantation (BMT) from an HLA identical donor, following cytoreduction with cyclophosphamide and total body irradiation (TBI): 15 were transplanted in 1st remission, 43 in 2nd and 7 in 3rd or in 4th. The Kaplan Meier estimate of surviving disease free at 4 years post BMT was 49.9% and the probability of continued remission at 4 years was 63.3%. Fourteen patients relapsed between 90 and 690 days (mean: 240 +/- 88) post BMT. The other causes of BMP failure included: graft versus host disease, veno-occlusive disease and sepsis. No interstitial pneumonitis has been reported. Patients who had a relapse while on chemotherapy had a higher probability of relapse than those who had a relapse while off therapy (p less than 0.01). We conclude that allogeneic BMT is the treatment of choice for children with ALL in second hematologic remission, the interval between diagnosis and first relapse being the most significant prognostic factor. Patients with poor prognosis might benefit from a more intensive chemotherapy/total body irradiation schedule or a BMT earlier in the course of their disease.     

CRANIAL COMPUTED TOMOGRAPHY DURING TREATMENT OF CHILDHOOD LYMPHOCYTIC LEUKEMIA

ABSTRACT. Twenty-three children with acute lymphocytic leukemia (ALL) were examined by computed tomography (CT) of the head on two occasions more than 11 months apart. The first CT was performed at the time of diagnosis in 11 children, who were re-examined while still in their first complete remission. They had received prophylactic central nervous system (CNS) treatment consisting of intrathecal methotrexate supplemented by irradiation in 7 cases and intermediate dose methotrexate in 4 cases. Twelve children were receiving treatment for CNS relapse. This included therapeutic irradiation and intrathecal methotrexate. Abnormal CT developed in 7 children. Three CT scans demonstrated areas of decreased attenuation coefficient, one with intracerebral calcifications. In 5 patients, dilatation of the ventricles and cortical sulci had developed. AU CT abnormalities occurred in children in remission after CNS relapse. These results indicate that prophylactic treatment including cranial irradiation with 24 Gy and low cumulative doses of methotrexate is a safe procedure. Patients with CNS leukemia are at risk of developing CNS abnormalities, when they receive treatment with cranial irradiation and methotrexate. The risk is not correlated with age or sex of the child, the duration of the disease, the dose of irradiation or the cumulative dose of methotrexate.     

Relapses after termination of therapy of acute lymphoblastic leukemia in children

In the past 16 years, 2004 children with acute lymphoblastic leukemia (ALL) have been treated in the Polish Pediatric Group centers. Eight hundred and eighty-seven (44.3%) of these patients discontinued treatment after the first remission. Acute lymphoblastic leukemia relapse occurred in 180 patients (20.3%). This group was analyzed for the method of treatment and its influence on long-term survival, the time between cessation of treatment and relapse, the character and localization of relapse and later follow-up. It was shown that the patients with the best chance of a second remission are those with late testicular relapse. The most frequent and prognostically poor are bone marrow (BM) relapses which warrant intensive chemotherapy with BM transplantation. Patients with ALL relapse still have the possibility of a second remission and long-term survival.     

小儿急性白血病外周血白细胞介素Ⅱ活性的测定及临床意义

小儿急性白血病外周血白细胞介素Ⅱ活性的测定及临床意义郭承吉，王巍中国医科大学第一临床学院杨晓玲，周正任微生物教研组白细胞介素Ⅱ（ＩＬ－２）是免疫系统中重要的淋巴因子，在体内外具有许多免疫调节特性，在一些血液病的发生、发展及治疗中起一定作用。我们检测了...