Lack of prognostic value of T-, B- and null-lymphocytes in adult acute leukemia

The distribution of T-, B- and null-lymphocytes was studied in the peripheral blood of 38 adult patients with acute nonlymphocytic leukemia (ANLL) and 15 with acute lymphocytic leukemia (ALL) at first diagnosis, during induction treatment, and in remission. Thirteen ANLL and 9 ALL patients were followed until relapse and during reinduction therapy. T- and B-cells were detected by specific membrane marker. The pre- and posttreatment pattern of lymphocyte subpopulations was analyzed to determine their prognostic significance for remission incidence, remission duration, and survival. It was observed that in both types of leukemia, T-cells are more affected by the leukemic process and cytostatic drugs than B-cells. Nonresponding patients possibly have a reduced potential for recruiting precursor T- and B-cells. At first diagnosis, no significant correlation was found between pre- or posttreatment variables and prognosis. At relapse, ANLL patients had a longer second remission when a high proportion of B-cells was found; ALL patients with a high lymphocyte count before and after treatment, experienced longer survival.     

497例儿童少年急性白血病髓外浸润特点

目的 　分析儿童少年急性白血病 (AL)髓外浸润临床特点 ,指导临床治疗 ,提高长期生存率。方法 　回顾性分析 4 97例儿童少年AL ,为 1 996年 5月～ 2 0 0 3年 5月我院初诊住院的急性白血病患儿。结果 　 1 7岁以下儿童少年AL中 ,ALL占 6 3% ,ANLL 33%。ALL初诊者髓外浸润中以纵隔浸润最多见 ,并多见于T -ALL患儿。髓外浸润在ALL高危组中的发生率最高。ANLL初诊时的髓外浸润常见部位为CNS、皮肤、眼部、胸膜等 ,多发生于M2b、M4 和M5型患儿。初诊时CNS浸润ANLL比ALL常见 ,中位年龄 1 2岁 ,男性高白细胞者多发 ,发生CNS浸润最常见的是M2b型 ,均有染色体t( 8;2 1 )异常。治疗中髓外复发主要在ALL患儿的CNSL ,发病率 1 4 .5%。结论儿童少年AL髓外浸润多见于T -ALL及M2b患儿 ,与预后不良有关。早期发现 ,积极治疗 ,可降低儿童少年AL的CNSL发病率。     

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.     

Infant leukemia in Japan: clinical and biological analysis of 48 cases

Forty-eight Japanese infants with acute lymphoid leukemia (ALL) (n = 24) and acute nonlymphoid leukemia (ANLL) (n = 24) were analyzed on the basis of clinical and laboratory data. Morphologically, 20 of the 24 infants with ALL were of the FAB L1 type, and 20 of the 24 infants with ANLL were of the M4 or M5 type. Markedly enlarged liver and spleen, and hyperleukocytosis (more than 50,000/microliters) were seen in 9, 12, and 14 infants with ALL and 10, 11, and 10 infants with ANLL, respectively. Initial CNS leukemia was evident in 2 infants. Chromosome studies of the leukemic cells showed abnormal karyotypes in 9 of the 21 infants with ALL and 19 of the 22 infants with ANLL, consisting mainly of translocation 11, 12, and inversion 16. By surface marker analysis, only 7 of the 22 infants with ALL (32%) were diagnosed as having common ALL (HLA-DR+, CD19+, CD10+). Of the 15 infants with ANLL, 12 and 5 infants also showed reactivity to HLA-DR and CD19, respectively. All of the 5 ANLL infants with lymphoid markers showed different leukemic cell features at the time of relapse. Twelve of the 19 infants with ALL (63%) who achieved a complete remission relapsed within the first 2 years; 8 of the 21 with ANLL (38%) relapsed within the first year. Analysis of event-free survival shows that the ALL infants with hyperleukocytosis have a poorer prognosis than those without hyperleukocytosis (p less than 0.05). Infant leukemia originates in a multipotent cell with lymphoid and myeloid features, and intensive multiagent chemotherapy is necessary for the treatment of infants with acute leukemia.     

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.     

Induction therapy of acute leukemia in children. Current results and problems related to therapeutic aplasia. Apropos of 146 cases

Between 1983 and 1984, 146 children have been treated in the pediatric hematology department of Saint-Louis Hospital (Paris) for induction of acute leukemia (AL). 119 had an acute lymphocytic leukemia (ALL) and 27 an acute non lymphocytic leukemia (ANLL). The rate of complete remission was 94% for all patients (97% in ALL and 81.5% in ANLL). Fever occurred in 95% of children with positive blood cultures in one third on these. Four children died between the fifth and the twenty fifth days after onset of treatment from sepsis. One of these patients was a neonate with ANLL. 127 patients had a central venous line during induction used for blood sampling and treatment (chemotherapy, antibiotics, parenteral nutrition, platelets and red blood cells infusions). This supportive care is very important to improve prognosis of the AL particularly in very intensive chemotherapy.     

HbF与儿童急性白血病的预后

本文用抗硷血红蛋白法测定了３９例急性白血病患儿胎儿血红蛋白（ＨＢＦ）含量。结果示：２９例急性淋巴细胞白血病（Ａｌｌ）ＨｂＦ平均值为３．１５％，１０例急性非淋巴细胞白血病（ＡＮＬＬ）ＨｂＦ平均值为５．２１％，均有轻度增高，且经统计学处理，ＡＮＬＬ较ＡＬＬ为高，差异有显著性意义；相关分析示ＨｂＦ含量与缓解后初次复发的时间的负相关关系有显著意义；发病危险度的估计表明ＨｂＦ水平与急性白血病复发或死亡之间存在非常显著性关系。     

Serum LDH values in childhood acute leukemias and non-Hodgkin's lymphoma

Serum lactate dehydrogenase activity (LDH) was examined in 66 children with acute lymphoblastic leukemia (ALL), 26 with acute non-lymphocytic leukemia (ANLL), and 116 with non-Hodgkin's lymphoma (NHL). The mean serum LDH value for the ALL and ANLL groups was not significantly different: 970 +/- 105 units/L (mean +/- standard error of the mean) and 817 +/- 161 units/L, respectively. The difference between the LDH values in patients with ALL (970 +/- 105 units/L) and NHL (551 +/- 51 units/L) was significant (P = .001). In 32% of the patients with ALL and 23% of the patients with ANLL, serum LDH values were above 1000 units/L, whereas only 13% of the cases with NHL had values above 1000 units/L. In patients with ALL the LDH levels were correlated with white blood cell counts at the time of diagnosis. In NHL, there was no difference in serum LDH levels among the various histologic subtypes. Values of LDH in stage IV NHL and in ALL were similar.     

Growth patterns and final height of survivors of childhood leukemia

Growth patterns of 85 survivors of childhood leukemia were analyzed retrospectively. All patients remained in first remission with no central nervous system involvement. The mean age at diagnosis was 5.8 +/- 3.6 years. The diagnoses were acute lymphoblastic leukemia (ALL) in 68 patients (80%) and acute non-lymphoblastic leukemia (ANLL) in 17 patients (20%). All except two patients received cranial irradiation: 51 patients with 1,800 cGy and 32 patients with 2,400 cGy. Mean height SDS was -0.7 +/- 1.36 at the time of diagnosis, which decreased to -0.92 +/- 1.31 by the end of treatment, and further decreased to -1.14 +/- 1.38 at 6 years after cessation of treatment. Mean weight SDS was -0.55 +/- 1.13 at the time of diagnosis, increasing slightly to -0.39 +/- 1.02 at the end of treatment, and decreasing to -0.46 +/- 1.65 at 6 years after cessation of treatment. Of these survivors, 51 patients (26 boys and 25 girls) reached a final height that was 1.04 SDS or 5.3 cm less than their target height. There was no difference of height and weight SDS between patients with ALL and ANLL. Girls and boys had different growth patterns. Girls had a slightly increased height SDS and gained more weight after cessation of treatment, resulting in less final height deficit and overweight for height, whereas boys had further height and weight reduction resulting in more deficit of final height.     

INCIDENCE OF CHILDHOOD LEUKEMIA IN SWEDEN 1975-1980

ABSTRACT. During the six-year period 1975-1980, leukemia was diagnosed in 466 children in Sweden, giving an estimated incidence of 4.4/100000 children per year (0-15 years at diagnosis). The incidence of acute lymphoblastic leukemia (ALL) was 3.7, of acute nonlymphocytic leukemia (ANLL) 0.6 and of chronic myelocytic leukemia (CML) 0.1/100000 children per year. The over all incidence among boys was 4.5/100000 per year and among girls 4.2. The male:female ratio was 1.13. This ratio was 1.22 in ALL and 0.71 in ANLL. Fifty per cent of the children were below 5 years of age at diagnosis, with a pronounced peak between 2-3 years, which was explained by the ALL distribution. In children with acute leukemia 13% had WBC values of >100×10⁹l, 4% had CNS leukemia and 10% had a mediastinal mass at diagnosis. The geographical distribution of leukemia in Sweden was analysed in a search for clusters of cases.     

Prognostic factors for relapsed childhood acute lymphoblastic leukemia: impact of allogeneic stem cell transplantation--a report from the Kyushu-Yamaguchi Children's Cancer Study Group

BACKGROUND: The treatment results of childhood acute lymphoblastic leukemia (ALL) with a first relapse were retrospectively analyzed to determine prognostic factors. In particular, an attempt was made to clarify whether stem cell transplantation (SCT) had any advantages over chemotherapy. PROCEDURES: Of the 407 children with ALL diagnosed between 1984 and 1996, 117 suffered from a relapse before December 1999. The patients were treated differently according to the protocols of each institution. The potential prognostic factors examined were: the time of initial diagnosis, gender, immunophenotype of leukemic blasts and the NCI-risk classification at initial diagnosis, the site of relapse, the time of relapse (early: within 18 months after diagnosis, intermediate: other than either early or late relapse, late: later than 6 months after the discontinuation of front-line chemotherapy), and the treatment after relapse (chemotherapy alone and SCT). RESULTS: A second complete remission (CR2) was achieved in 90 patients (77%) and thirty of them maintained CR2, thus resulting in an event-free survival rate (EFS) of 25.1% and an overall survival rate of 26.1%. The significant prognostic factors identified by a multivariate analysis included the time of relapse (EFS: early 16.2%, intermediate 23.9%, late 35.1%, P = 0.012) and the treatment after relapse (EFS: SCT 30.3%, chemotherapy 22.0%, P = 0.049). When patients with an isolated bone marrow relapse and continuous CR2 for more than 3 months were analyzed, the treatment in CR2 was the only independent prognostic factor (EFS: SCT 60.2%, chemotherapy 25.7%, P = 0.005). CONCLUSIONS: In children with ALL and a first relapse, the time of relapse and the treatment after relapse were found to be independent prognostic factors. Allogeneic SCT in CR2 showed significantly better results than chemotherapy in patients with an isolated bone marrow relapse.     

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.     

Serum soluble L-selectin in childhood acute lymphoblastic leukemia

BACKGROUND: Determination of the serum level of soluble (s)L-selectin has been advocated for monitoring patient response to treatment in leukemia. The aim of the present study was to find out whether serum levels of sL-selectin correlated with treatment for acute lymphoblastic leukemia (ALL) in children. METHODS AND RESULTS: Serum samples were obtained from 30 children with ALL, either newly diagnosed during induction therapy, in remission, in maintenance therapy, at the end of treatment or after relapse. Levels of sL-selectin were assayed in the serum of children during the clinical course of ALL using the sandwich enzyme-linked immunoabsorbent assay. Serum sL-selectin concentrations decreased significantly from diagnosis to the end of intensive chemotherapy in children with ALL and increased in the time of relapse. CONCLUSION: These results suggest that monitoring of sL-selectin may be useful for evaluating leukemia activity.     

A phase II study of diaziquone in childhood leukemia: a report from the Children's Cancer Study Group

Diaziquone (aziridinylbenzoquinone, AZQ) was given by 30-min infusion at 25 mg/m2/day on a daily x 5 schedule to 16 children with acute lymphoblastic leukemia (ALL) in bone marrow relapse, 16 children with acute nonlymphocytic leukemia (ANLL) in bone marrow relapse, and 1 child with chronic myelocytic leukemia in blast crisis. None of the children achieved bone marrow remission. Five children (four with ALL and one with ANLL) were also evaluable for the response of central nervous system leukemia; all had a significant reduction in the cerebrospinal fluid blast count. Mild transient transaminase elevation was commonly seen. Grade 3 and 4 hyperbilirubinemia was seen in association with sepsis. AZQ was ineffective for induction of bone marrow remission as utilized in this study.     

Immunological Classification of Childhood Acute Lymphoblastic Leukemia

Seven hundred and forty-four newly diagnosed patients with acute leukemias between 1978 and 1990 were classified on the basis of immunological phenotypes. The majority of the patients were enrolled in the Tokyo Children's Cancer Study Group (TCCSG) studies. The incidence of subclassification of acute leukemias in this study was as follows: 522 patients with ALL (70%), 139 patients with ANLL (18%), 29 patients with biphenotypic leukemia, 8 patients with Ph1-positive acute leukemia (Ph^-AL), and 45 patients with infant leukemia. ALLs were classified into common ALL (cALL, 77%), T-ALL (15%), B-ALL (4%), and unclassified ALL (3%). The incidence of ALL subtypes in this study reflected those of TCCSG. Biphenotypic leukemias were categorized into 4 groups as follows; 1) cALL with positive myelomonocytic antigen(s) (N = 11), 2) unclassified ALL with positive myelomonocytic antigen(s) (N = 5), 3) ANLL with positive B-lymphoid antigen(s) (N = 4), and 4) acute leukemia with positive T-lymphoid and myeloid antigen(s). Infant leukemias were classified into ALL type (N = 27) and ANLL type (N = 18). In this present study, clinical features and immunological phenotypes of the acute leukemias with a poor prognosis, i.e. biphenotypic leukemia, Ph^-AL, and infant leukemia are analyzed and discussed.     

Elevated production of interleukin-2 by lymphocytes from children with acute leukemia

Abnormalities of the production of interleukin-2 (IL-2) may play an important role in the immunologic dysfunction observed in pediatric leukemia patients. For an evaluation of the ability of lymphocytes from leukemic children to produce this cytokine, the production of IL-2 by mitogen-stimulated peripheral blood mononuclear cells was determined in children with acute leukemia at the time of diagnosis, during clinical remission, and at the time of relapse. Of 16 patients, 11 (69%) with either acute lymphoblastic leukemia or acute nonlymphoblastic leukemia at the time of diagnosis had IL-2 production levels above the highest level observed in control subjects, and all but one had values above the control mean. Three of five treated patients had elevated IL-2 production at the time of bone marrow relapse. In addition, of 37 patients examined during clinical remission (both during chemotherapy and after the completion of maintenance chemotherapy), five had IL-2 production values above the control range and four of these five patients subsequently had relapses, compared with only one relapse in the remaining 32 patients with normal or below-normal levels of IL-2 production. These results demonstrate an increased ability to produce IL-2 by many patients with acute leukemia, both at the time of diagnosis and at relapse. Elevated IL-2 production may represent an immunologic response to leukemic cells and in some patients may provide a marker for persistent leukemia.     

Acute megakaryoblastic leukemia in children identified by immunological marker studies

Acute megakaryoblastic leukemia (AMkL), defined by the presence of the platelet-associated glycoprotein IIb/IIIa complex on malignant cells, was diagnosed in 4 (4%) of 103 consecutive children with untreated acute leukemia or 4 (21%) of 19 children with acute nonlymphoblastic leukemia (ANLL). Particular features in the four children with AMkL were an age below 12 months at diagnosis (two patients), the absence of a significant hepatosplenomegaly (three patients), a leukocyte count below 20 x 10(9)/L with only a few blast cells in the peripheral blood (four patients), a technically difficult bone marrow aspiration (three patients), the presence of many megakaryocytes in marrow particles (two patients), and an inconclusive cytochemistry (four patients). The four children with AMkL were treated according to protocols for ANLL and a complete remission was obtained in all patients. One patient died from relapse after 3 months, one patient is a long-term survivor (38+ months), and two patients still on chemotherapy are disease-free for 11+ and 13+ months.     

Allogeneic bone marrow transplantation versus chemotherapy in children with acute leukemia in Sweden

All children in Sweden who underwent bone marrow transplantation (BMT) with an HLA-identical sibling during a 5-year period were compared to those who were treated with chemotherapy and survived at least 3 months after remission. All patients were observed for more than 2 years after diagnosis or relapse. All 11 children with acute myeloid leukemia in first remission who underwent BMT survived compared to only 1 of 15 treated with chemotherapy (p less than 0.001). In children with acute lymphoblastic leukemia (ALL), those relapsing while on chemotherapy and treated with BMT in second to fourth remission (n = 16) had a 5-year survival of 43% compared to 16% for those treated with chemotherapy (n = 53, p less than 0.05). In children with ALL relapsing after cessation of therapy, 4-year survival was 33% for BMT (n = 6) and 55% for chemotherapy (n = 15), p = 0.05).