Gonadal function after chemotherapy for acute lymphoblastic leukemia

Object of this study was to verify long term effects on gonadal function in pre- and pubertal patients affected by acute lymphoblastic leukemia (ALL). The population examined was represented by 15 patients, 10 males and 5 females, who came to our Unit after a period of time ranging from 4.5 to 6.2 years. All the patients underwent combined chemotherapy without alkylating agents, such as cyclophosfamide and citosine arabinoside, and intrathecally radiotherapy for a mean period of two years. All the patients were off-therapy and without symptoms of relapse except for one case. The examination of the male and female gonadal function was done on the basis of hormonal assay, ultrasonographic examinations, Tanner's determination of the pubertal development, monitoring of the ovulation and seminal fluid evaluation. The clinical results obtained showed an absence of negative effects both on the gonadal function and on pubertal development. Combined chemotherapy for ALL during pre- and pubertal stage without alkylating agents does not alter the normal gonadal function during the following ten years. Prospective studies will establish the risk of partial follicular atresia and the incidence of premature gonadal failure.     

改良的德国多中心成年人急性淋巴细胞白血病研究组方案临床应用研究

目的 分析改良的德国多中心成年人急性淋巴细胞白血病研究组(GMALL)方案治疗成年人急性淋巴细胞白血病(ALL)的疗效和安全性.方法 2005年1月至2009年12月共37例新诊断的ALL患者,接受改良的GMALL方案单纯化疗,对其进行回顾性分析,并与同期接受该院常规方案治疗的44例成年ALL患者进行对比分析.结果 改良GMALL方案的累积完全缓解(CR)率为89.2%(33/37),1、2、3及4年累积总生存(0S)率分别为77.5%、48.0%、40.0%和40.0%.主要不良反应为3～4级血液学毒性和感染,不良反应易于控制,治疗相关死亡率低.改良GMALL方案组的OS优于该院常规方案组.结论 改良的GMALL方案治疗成年人ALL疗效满意,不良反应可以耐受,值得临床推广.     

Beta-1-integrin expression in adult acute lymphoblastic leukemia: possible relationship with the stem cell antigen CD34

In the hemopoietic system, interactions between stem cells and components of the bone marrow microenvironment play a pivotal role in blood cell proliferation and differentiation. Among the adhesion molecules, the integrins of the beta 1-subfamily are known to direct cell-cell and cell-matrix interactions and evidence has been provided that CD34-positive stem cells bind either to the bone marrow stroma or to the extracellular matrix proteins through the beta 1-integrins. It seems that changes in their expression pattern or signalling function are likely to reflect disturbances at the hemopoietic bone marrow microenvironmental level. Any alteration of their biological functions makes them attractive candidates for playing decisive roles in the leukemic processes. In this view, beta 1-integrins have been recognized to mediate those cellular interactions and migrations that are important in the biology of leukemia. In this paper we review some aspects of the role played by beta 1-integrins, especially VLA-4 and VLA-5, in adult acute lymphoblastic leukemia in relation with the expression rate of the stem cell antigen CD34.     

The hyper-CVAD regimen improves outcome in relapsed acute lymphoblastic leukemia

Sixty-six adults with refractory acute lymphocytic leukemia received salvage therapy with the 'hyper-CVAD' regimen, consisting of eight courses of alternating intensive chemotherapy with growth factor support, followed by oral maintenance chemotherapy. Their outcome was compared with 63 prognostically similar historical control patients treated with high-dose Ara-C plus mitoxantrone with or without GM-CSF. Overall, the complete response rates were similar in the treatment and control groups (29 of 66 (44%) vs 24 of 63 (38%)). There were more patients in the current study with primary resistant disease (10 of 66 (15%) vs one of 63 (2%), P = 0.006), and conversely fewer patients with secondary resistance (19 of 66 (29%) vs 28 of 63 (44%), P = 0.06). Recovery of granulocyte counts above 500/microl was significantly faster in the current study when compared to high-dose Ara-C-treated patients who were given GM-CSF (20 vs 25 days, P = 0.04). Survival was prolonged in the hyper-CVAD-treated patients, with most of the benefit seen in first salvage patients (42 vs 20 weeks, P = 0.016). When only first salvage patients were considered, there was a significant difference in disease-free survival in favor of hyper-CVAD (52 vs 20 weeks, P = 0.008). The hyper-CVAD regimen is a more effective and less toxic salvage regimen for relapsed acute lymphocytic leukemia than high-dose Ara-C-based regimens.     

Testicular morphological changes in children with acute lymphoblastic leukemia following chemotherapy

Morphological changes in the testis induced by chemotherapy given according to the Tokyo Children's Cancer Study Group (TCCSG) regimens were studied in children with acute lymphoblastic leukemia (ALL). After informed consent, testicular biopsies were performed 14 times in 12 patients at the end of treatment. The testicular morphology in all cases had sustained a degree of damage. The tubular fertility index (TFI), calculated as the percentage of seminiferous tubules containing identifiable spermatogonia, was from 0 to 42.8% (mean 33.4%) below the normal value. Infiltration of leukemic cells was the most significant factor contributing to the decrease in TFI. There were no differences in the TFI among the TCCSG protocols. Formation of sperm was recognized in six cases, whose ages were 7, 8, 9, 10, 15 and 19 years. In two children, testicular biopsy was performed twice. In the second biopsy, TFI was elevated and sperm formation with the maturation of Leydig cells was observed. A number of other pathological changes were observed: modification of spermatogonia, Sertoli cells and inclusion bodies in spermatogonia, abnormal maturation of Leydig cells, evidence of interstitial fibrosis and thickening of the basement membrane. These results suggest that recent strong chemotherapy for the treatment of ALL might cause severe but not fatal damage to children's testicular tissue. As chemotherapy escalates, more investigation of testicular function will be necessary.     

Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group

In acute myelogenous leukemia (AML) intensive postremission treatment is needed for an optimal result. However, it is not known how long the treatment should last and how many courses are necessary. The object of this prospective study was to compare four and eight intensive chemotherapy cycles in the treatment of adult de novo AML. In a multicenter study, 248 consecutive patients, aged from 16 to 65 years, were treated with intensive induction treatment. The patients in remission after two courses were randomized to receive either two (short arm) or six (long arm) additional intensive cycles of chemotherapy. The median follow-up time of the living patients is 68 months. Of the patients, 77% achieved complete remission, and 36% of all patients survived for 5 years. Seventy-three patients were randomized to the short arm and 66 to the long arm. There was no significant difference in the relapse-free survival (median 21 months vs 17 months) or overall survival (43 months vs 39 months) between the short and long arms, respectively. Treatment-related deaths occurred in 31 patients (13%), 11 of them in first remission. More than one-third of the patients survived for 5 years. It seems probable that the first few months after diagnosis are decisive for the prognosis if the chemotherapy is intensive, and further treatment cannot markedly influence the outcome.     

成年人伴CD2表达B系急性淋巴细胞白血病免疫表型特征分析

目的 了解成年人伴CD2表达B系急性淋巴细胞白血病(CD+2 B-ALL)的免疫表型特征,为临床诊断、治疗及预后判断提供依据.方法 应用流式细胞术及多种单克降抗体检测18例成年人CD+2B-ALL及68例CD-2 B-ALL患者的免疫表型,并对其结果进行分析比较.结果 CD+2 B-ALL的发病年龄明显小于CD-2 B-ALL,18例成年人CD+2 B-ALL的大部分表面标志物与CD-2 B-ALL相似,其中CD10表达水平[(73.78±26.67)%]高于CD-2 B-ALL[(52.84±35.25)%],差异有统计学意义(t=2.35,P<0.05),CD33表达水平[(15.46±27.41)%]则低于CD-2 B-ALL[(31.15±27.72)%],差异有统计学意义(t=2.16,P<0.05);所有B-ALL患者都高表达CD34,阳性表达率分别为72.2%(13/18)和80.9%(55/68),差异无统计学意义(χ2=0.64,P>0.05).CD+2 B-ALL的CD20阳性率明显低于CD-2 B-ALL,差异有统计学意义(χ2=11.38,P<0.05).CD+2 B-ALL伴髓系抗原(CD13或CD33)表达率为44.4%(8/18),明显低于CD-2 B-ALL的72.1%(49/68),差异有统计学意义(χ2=4.86,P<0.05).结论 成年人CD+2 B-ALL与CD-2 B-ALL具有相似的免疫表型,主要来源于造血干细胞的恶性转化,CD+2 B-ALL伴髓系抗原(CD13、CD33)及CD20表达明显低于CD2 B-ALL,提示成年人CD+2 B-ALL可能有较好的预后.     

Low frequency of TEL/AML1 in adult acute lymphoblastic leukemia

Translocation (12;21)(p13;q22) is a recently characterized aberration in acute lymphoblastic leukemia, and results in the fusion of the TEL and the AML1 genes. It is the most common translocation in pediatric acute lymphoblastic leukemia (ALL), occurring in about one third of the cases. To determine the frequency of TEL/AML1 in adult ALL, we studied 4 cases of T lineage ALL and 26 cases of B lineage ALL. Only one positive case was identified, giving a very low frequency of 3.3%. In this patient, TEL/AML1 was still detectable in complete hematologic remission. The apparent age predilection of t(12;21) warrants further investigations.     

Clostridium septicum sepsis and neutropenic enterocolitis in a patient treated with intensive chemotherapy for acute myeloid leukemia

A retinal dopaminergic deficiency underlies some visual changes in Parkinson's disease (PD), in particular those elicited by stimuli near the peak of the human and monkey spatial contrast sensitivity. The correspondence of retinal changes and VEP alterations is not perfect: they do not seem to rely on identical mechanisms. It seems that additional pathology beyond the retina affects visual responses, including VEPs. The relevance of "distal" primary VEP changes to higher cognitive visual abnormalities in PD is not established at present.     

CD7 positive acute lymphoblastic leukemia successfully treated with high dose cytosine arabinoside and mitoxantrone: a case report

Primary Sjogren's syndrome (pSS) is a common autoimmune connective tissue disease in China yet without a universally accepted diagnostic criteria. In this study a new criteria was proposed and compared with other six sets of criteria. Fifty-five items in 112 pSS and 185 controls were evaluated. Results show the criteria we proposed contained one major and nine minor items. For the purpose of identifying patients in clinical studies, a major with at least three of the nine minor items or at least five of the minor items should be presented. The major item is anti-SSA/SSB(+) and the minors are, (1) dry eyes or dry mouth (> 3 months, persistently), (2) swollen salivary glands (recurrently or persistently), (3) rampant dental caries, (4) Schirmer test (< 5 mm in 5 min.) or corneal staining(+), (5) unstimulated salivary flow (< 0.03 ml/min) or abornal parotid sialography, (6) minor salivary gland biopsy (> or = 1 focus), (7) renal tubular acidosis, (8) hypergammaglobuminemia (gamma globulin > or = 30%) or hypergammaglobuminemic purpura, (9) RF > 1 : 20 or ANA > 1 : 20. Other connective tissure diseases, pre-existing lymphoma, AIDS, sarcoidosis, graft vs host disease must be excluded. The criteria we proposed had a high specificity of 98.2% and sensitivity of 94.1%.     

CD20在成年人急性B淋巴细胞白血病中的表达及其临床意义

目的 检测CD20在成年人急性B淋巴细胞白血病(B-ALL)的表达,探讨其与临床特点的相关性.方法 回顾性总结分析96例成年B-ALL患者CD20表达情况,结合其临床特性和治疗转归进行分析.结果 96例成年B-ALL患者中,CD20阳性29例(30.20%),CD20阴性67例(69.79%).CD20阳性组与阴性组男女比分别为1.42∶1和1.79∶1(x2=0.27,P＞0.05),中位年龄分别为28岁与23岁,肝脾及淋巴结浸润比例分别为44.83%和41.38%、40.30%和35.82%,髓系抗原表达比例分别为51.72%与56.72%,Ph染色体和bcr-abl融合基因阳性比例分别为24.14%与28.36%,4周内完全缓解率分别为73.08%与68.85%,差异均无统计学意义(P值均＞0.05).在复发率和3年总体生存率上,CD20阳性组分别为54.55%与14.80%,CD20阴性组分别为29.63%与37.30%,两组间差异有统计学意义(x2=0.42,x2=5.31;P值均＜0.05).结论 CD20在成年人B-ALL表达与临床特点无相关性,但对判断患者的预后有一定的指导意义.     

Dental abnormalities in children treated for acute lymphoblastic leukemia

The purpose of this study was to define the therapy-associated dental abnormalities in survivors of acute lymphoblastic leukemia (ALL). We reviewed the clinical records and panoramic radiographs of 423 survivors of ALL who were treated on one of four consecutive protocols (1975-1991). Dental abnormalities included root stunting, microdontia, hypodontia, taurodontia (enlarged pulp chambers), and over-retention of primary teeth. The frequency of these factors was determined in relation to age at initiation of treatment (< or = 8 years vs > 8 years), addition of cranial irradiation, and chemotherapeutic protocol. A total of 423 patients met the study criteria. The abnormalities comprised root stunting in 24.4% (n = 103), microdontia in 18.9% (n = 80), hypodontia in 8.5% (n = 36), taurodontia in 5.9% (n = 25), and over-retention of primary dentition in 4.0% (n = 17). Patients who were < or = 8 years old at diagnosis or who received cranial irradiation therapy developed more dental abnormalities than did those > 8 years and those who did not receive cranial irradiation (42 vs 32%). Survivors of childhood ALL often have dental abnormalities that may affect their quality of life. Dental evaluation at diagnosis and frequent follow-up may help to ensure appropriate preventive measures and minimize dental and periodontal disease.     

Pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy: outcome and prognostic factors

STUDY OBJECTIVE: To determine predictors of mortality from pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy, and the significance of those factors related to the underlying malignancy and its therapy as well as of those related to the severity of the illness associated with pulmonary infiltrates. DESIGN: A historical cohort study. SETTING: A university teaching hospital and tertiary referral center. PATIENTS AND METHODS: Overall, 53 patients with neutropenia during chemotherapy and with first episodes of pulmonary infiltrates during a 4-year period were studied. Prognostic analysis included 38 variables. Multivariate analyses were performed by logistic regression. RESULTS: The survival rate from pneumonia was 57% (30/53). The following eight parameters were significantly associated with death in univariate analysis: comorbidity present; development of "late" pulmonary infiltrates (> or = 14 days after hospital admission); heart rate > or = 100 beats/min; a ratio heart rate/systolic blood pressure (HR/SBP) > or = 1.2; urea nitrogen > 7 mmol/L; radiographic score > or = 3; neutropenia < 1.0x10(9)/L at the treatment end point; and failed complete remission. In a multivariate model including only parameters available at diagnosis of pulmonary infiltrates, the presence of a ratio HR/SBP > or = 1.2 and of a radiographic score > or = 3 remained independently associated with death. In a second model also including the evolutionary parameter neutropenia < or = 1.0x10(9)/L at the treatment end point, both parameters remained significant together with neutropenia <1.0x 10(9)/L at the treatment end point. The presence of a ratio HR/SBP > or = 1.2 was a strong marker of early death. CONCLUSION: Both therapy- and malignancy-associated neutropenia as well as the severity of illness associated with pulmonary infiltrates are independent prognostic factors. Patients with a ratio HR/SBP > or = 1.2 at diagnosis of pulmonary infiltrates suffer from potentially reversible acute illness, are at risk for early death and, therefore, may be appropriate candidates for treatment in an ICU.     

Transient hyperphosphatasemia observed in a boy with acute lymphoblastic leukemia

A detailed time course of alkaline phosphatase (ALP; EC3.1.3.1) activity of transient hyperphosphatasemia (TH) in a 9-year-old boy with acute lymphoblastic leukemia (ALL) is described. The patient's serum ALP activity rose transiently to 49 times the upper limit of normal adult, without any evidences of hepatic and bone disease. The half-life of ALP activity was calculated about 10 days. We characterized ALP isoenzymes by usual electrophoresis using cellulose acetate membrane (Titan III iso-vis) and polyacrylamide disc gel (AlkPhor), and isoelectric focusing using polyacrylamide slab gel. The former two methods showed typical two bands (fast-alpha 2 and alpha 2 beta bands) and the latter one method revealed more basic bands of liver and bone, suggesting the extensive sialylation. The patient complained fever and diarrhea. Enterococcus faecium was detected from his stool. Etiologically, two more patients in the same ward showed TH in the same period. It suggested TH would be occurred by infectious states. Awareness of such benign forms of hyperphosphatasemia not related to malignancy will aid the physician in the differential diagnosis of elevated ALP activity.     

Philadelphia positive acute lymphoblastic leukemia 16 years after the apparent cure of acute lymphoblastic leukemia. New leukemia or late relapse?

A Philadelphia-positive ALL in an adult occurring 21 years after the initial diagnosis is reported here. This case raises the question as to whether or not this event is a relapse or a new leukemia. A possible role of interferon-alpha previously administered to the patient for a chronic viral hepatitis is discussed too.