转移癌患者血清转钴酶Ⅰ的异常升高

转钴酶Ⅰ(Transcobalamin Ⅰ)和血清维生素B_(12)升高通常与粒细胞增生有关。作者报告2例转移癌患者维生素B_(12)和转钴酶Ⅰ水平极度升高,甚至超过粒细胞增生时最高水平,故不能用粒细胞增生症解释。1例为胃小弯腺癌,合併肝转移患者,另一例为结肠癌合併肺、肝转移患者。2例患者白细胞数均未超过10,700/毫升,而血清维生素B_(12)水平分别达18,750和     

急性早幼粒细胞白血病缓解后多次髓外复发一例并文献复习

目的：探讨急性早幼粒细胞白血病（APL）复发的相关因素、治疗及预防。方法对1例多次复发的APL患者的临床资料进行回顾性分析,并复习相关文献。结果该患者2005年初诊为APL高危组,经诱导治疗后达完全缓解,随后进行巩固、维持治疗,其间未遵医嘱及早行鞘内注射预防中枢神经系统白血病,2011年复发,再次诱导治疗后完全缓解,并进行巩固维持治疗,2012年诊断中枢神经系统白血病,最终因髓外（皮肤、胃肠道）复发放弃治疗。结论对于APL高危组患者,应强调鞘内注射预防中枢神经系统白血病的重要性,同时应定期检测骨髓中PML-RARα融合基因以及时治疗,二次缓解后进行造血干细胞移植为治疗的重要手段。     

血清叶酸和同型半胱氨酸及维生素B12与男性食管癌发病风险相关性的研究

目的:探讨血清叶酸、维生素B12、同型半胱氨酸浓度与男性食管癌发病风险的相关性.方法:研究对象包括63例男性食管癌患者和63住男性健康对照者.食管癌组是从2006-08～2007-05在安徽省立医院就诊的食管癌患者,健康对照是在同一所医院查体的健康者.测定其血清叶酸、维生素B12和同型半胱氨酸浓度,然后通过统计学方法,比较食管癌患者血清中上述物质与健康人有无差异.结果:与血清叶酸、同型半胱氨酸、维生素B12水平最低的三分位人群相比,处于最高的三分位者惠食管癌的比值比(OR)分别是0.28(95 % CI:0.11～0.72,P=0.008)、4.62(95%CI 1.74～12.25,P=0.002)和2.61(95%CI:1.08～6.30,P=0.032).血清叶酸降低则食管癌发病率升高,而同型半胱氨酸和维生素B12在食管癌组较对照组升高.结论:血清叶酸与食管癌发病风险负相关,同型半胱氨酸和维生素B12与食管癌发病风险正相关.     

全反式维甲酸、6-巯嘌呤、甲氨蝶呤联合维持治疗急性早幼粒细胞白血病

目的 观察全反式维甲酸(ATRA)、6疏嘌呤(6-MP)、甲氨蝶呤(MTX)联合化疗方案对急性早幼粒细胞白血病(APL)完全缓解后维持治疗的疗效.方法 ATRA20mg,2次/d,连用15d,6-MP50mg,3次/d,连用15d,MTX 15mg,1次/周,2次.结果 39例患者中36例在观察期间获得血液学完全缓解(HCR)和分子学完全缓解(MCR),其中13例已完成维持治疗而停药未见复发.结论 ATRA、6-MP、MTX联合维持治疗APL复发率低,均可口服,实用、安全、方便、经济.     

长期生存的急性早幼粒细胞白血病PML/RARα融合基因的变化及意义

目的:观察长期生存的急性早幼粒细胞白血病(APL)PML/RARα融合基因的变化,探讨其临床意义。方法:运用筑巢式反转录聚合酶链(RT蛳PCR)方法,观察生存5 a以上的28例APL 的PML/RARα融合基因变化。结果:(1)初诊时10例PML/RARα融合基因测定9例阳性,阳性率90.0%。(2) 完全缓解后在不同时期阳性率测定结果:6个月时64.3 %,12 个月时46.7 %,24个月时31.6 %,36个月时25.0 %,48 个月时17.8 %,60个月时17.8 %。>60个月21.4 %。(3)3例60 个月时血象、骨髓为完全缓解状态,但PML/RARα融合基因阳性,其中2例62 个月、78 个月时复发。1例坚持化疗至96 个月时方转阴性,现持续缓解116 个月。3例PML/RARα融合基因由阴性转为阳性后复发。其余病例PML/RARα融合基因持续阴性,血象、骨髓完全缓解。(4)缓解后中止治疗的3例中,1例PML/RARα融合基因持续阳性在62 个月时复发死亡。2例由阴性转为阳性病例中1例在119 个月时复发死亡。1例CR 99个月复发,经白血康治疗后CR2。CR2 6个月时仍阳性。现生存112 个月。结论:长期生存的APL患者PML/RARα融合基因持续阳性或由阴性转为阳性常与复发有关。持续阴性常伴随长期无病生存。完全缓解后的维持治疗尚为一艰巨而长期的过程。对持续阳性病例,坚持长期、足够强烈的继续治疗,维持持续的首     

血清维生素B12水平与急性白血病的关联

目的：观察血清维生素B12（VitB12）的水平与急性白血病不同类型、不同疾病阶段的关联。方法：收集140例确诊为急性白血病的患者，其中急性髓系白血病（acute myeloid leukemia，AML）95例、急性杂合型白血病（hybrid acute leukemia，HAL）2例、急性淋巴细胞性白血病（acute lymphoblastic leukemia，ALL）43例，分成3组：初治组63例、第1次完全缓解（complete response，CR）组（CR1组）57例以及复发组20例。应用化学发光法检测3组患者血清VitB12的水平。结果：初治组中，血清VitB12水平的升高主要见于AML患者，尤其是M3患者。AML初治患者中血清VitB12水平升高者显著多于CR1的AML患者（P〈0．01）；AML复发患者中血清VitB12水平升高者也显著多于CR1组的AML患者（P〈0．01）。ALL初治患者与CRI患者相比，血清VitB12水平的差异无统计学意义（P〉0．05）；但ALL复发患者的血清VitB12水平升高者显著多于CR1的ALL患者（P〈0．01）。结论：VitB12是急性白血病的诊断指标之一，在急性白血病患者中存在血清VitB12水平的动态变化，血清VitB12水平的升高与疾病活动程度相关。     

亚砷酸、全反式维甲酸联合化疗治疗儿童急性早幼粒细胞白血病八例

目的 观察亚砷酸(As2O3)、全反式维甲酸(ATRA)联合化疗治疗儿童急性早幼粒细胞白血病(APL)的疗效.方法 8例APL患儿采用ATRA及柔红霉素(DNR)联合进行诱导、巩固及维持治疗,并定期检测PML-RARα融合基因.结果 完全缓解(CR)率为87.5%,达CR中位时间为26 d,并于巩固治疗期间采用As2O3与ATRA及蒽环类药物交替进行,并予以维持治疗,总疗程为3.5年.目前1例已停药,6例处于维持治疗阶段.7例患儿每3个月检测PML-RARα融合基因均为(-),仅1例患儿未达CR死亡.结论 As2O3与ATRA联合化疗治疗儿童APL的疗效较满意.     

亚砷酸、全反式维甲酸联合化疗治疗儿童急性早幼粒细胞白血病八例

目的 观察亚砷酸(As2O3)、全反式维甲酸(ATRA)联合化疗治疗儿童急性早幼粒细胞白血病(APL)的疗效.方法 8例APL患儿采用ATRA及柔红霉素(DNR)联合进行诱导、巩固及维持治疗,并定期检测PML-RARα融合基因.结果 完全缓解(CR)率为87.5%,达CR中位时间为26 d,并于巩固治疗期间采用As2O3与ATRA及蒽环类药物交替进行,并予以维持治疗,总疗程为3.5年.目前1例已停药,6例处于维持治疗阶段.7例患儿每3个月检测PML-RARα融合基因均为(-),仅1例患儿未达CR死亡.结论 As2O3与ATRA联合化疗治疗儿童APL的疗效较满意.     

亚砷酸、全反式维甲酸联合化疗治疗儿童急性早幼粒细胞白血病八例

目的 观察亚砷酸(As2O3)、全反式维甲酸(ATRA)联合化疗治疗儿童急性早幼粒细胞白血病(APL)的疗效.方法 8例APL患儿采用ATRA及柔红霉素(DNR)联合进行诱导、巩固及维持治疗,并定期检测PML-RARα融合基因.结果 完全缓解(CR)率为87.5%,达CR中位时间为26 d,并于巩固治疗期间采用As2O3与ATRA及蒽环类药物交替进行,并予以维持治疗,总疗程为3.5年.目前1例已停药,6例处于维持治疗阶段.7例患儿每3个月检测PML-RARα融合基因均为(-),仅1例患儿未达CR死亡.结论 As2O3与ATRA联合化疗治疗儿童APL的疗效较满意.     

亚砷酸、全反式维甲酸联合化疗治疗儿童急性早幼粒细胞白血病八例

目的 观察亚砷酸(As2O3)、全反式维甲酸(ATRA)联合化疗治疗儿童急性早幼粒细胞白血病(APL)的疗效.方法 8例APL患儿采用ATRA及柔红霉素(DNR)联合进行诱导、巩固及维持治疗,并定期检测PML-RARα融合基因.结果 完全缓解(CR)率为87.5%,达CR中位时间为26 d,并于巩固治疗期间采用As2O3与ATRA及蒽环类药物交替进行,并予以维持治疗,总疗程为3.5年.目前1例已停药,6例处于维持治疗阶段.7例患儿每3个月检测PML-RARα融合基因均为(-),仅1例患儿未达CR死亡.结论 As2O3与ATRA联合化疗治疗儿童APL的疗效较满意.     

Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia

BACKGROUND: From 20% to 30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) develop recurrent disease. Arsenic trioxide (ATO) is an effective agent for the salvage of patients with recurrent APL, and gemtuzumab ozogamicin (GO) has shown activity in patients with APL. METHODS: The authors investigated the efficacy of a combination of ATO, ATRA, and GO in 8 patients with APL in first recurrence (7 patients with hematologic recurrences and 1 patient with a molecular recurrence). All patients had received previous treatment with ATRA either alone or in combination with other agents. Patients received ATO 0.15 mg/kg intravenously until they achieved a bone marrow complete remission (CR). Once in CR, patients received consolidation with ATO, ATRA, and GO for 10 months. Patients then received maintenance with idarubicin, ATRA, 6-marcaptopurine, and oral methotrexate for 11 months. RESULTS: All 7 patients who had hematologic recurrences achieved CR after a median of 39 days (range, 21-56 days). After a median follow-up of >/=36 months (range, 4-55 months), 6 patients remained alive in CR, and 2 patients died in CR. Six of 8 patients remained in second CR that was longer than their first CR. All 7 evaluable patients achieved molecular remission. There were no grade 3 or 4 extramedullary toxicities. Two patients died, 1 secondary to a complication of metastatic lung adenocarcinoma, and the other of sepsis. CONCLUSIONS: The combination of ATO, ATRA, and GO was effective and may achieve durable remissions in patients with APL in first recurrence. It should be considered as an effective alternative to allogeneic or autologous transplantation.     

优福定联合叶酸片口服治疗晚期胃癌34例临床观察

目的　观察优福定(UFT)联合叶酸片口服治疗晚期胃癌的疗效。　方法　34例晚期胃癌,按不同的叶酸剂量分为A组18例(UFT12片/d;叶酸片60mg/d)B组16例(UFT12片/d;叶酸片30mg/d)。其中初治23例,复治11例。　结果　34例中,总有效率3825%。A组有效率3889%(完全缓解CR2例,部分缓解PR5例);B组有效率3750%(CR1例,PR5例)。两组疗效无明显差异(P>005)。有效病例中位缓解期4个月。本方案毒副反应小,患者能耐受。　结论　UFT联合叶酸片口服方案近期疗效高,毒副反应低     

All-transretinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia

BACKGROUND: All-transretinoic acid (ATRA) and chemotherapy has improved complete remission rates and disease free survival in acute promyelocytic leukemia (APL). There is scanty data from Middle East. AIM: To determine the efficacy of ATRA and multi-agent combination chemotherapy in treatment of APL in a single Centre in Kuwait. SET-UPS AND DESIGN: Tertiary cancer centre, retrospective study. METHODS AND MATERIAL: All newly diagnosed APL patients were treated with oral ATRA 45 mg/m2 daily until complete remission (CR), intravenous daunorubicin 50 mg/m2 on days 1,3 and 5, cytosine arabinoside 100 mg/m2 12 hrly on days 1 through 10 and etoposide 100 mg/m2 on days 1 through 5. Post remission three courses of intensive consolidation chemotherapy were administered. Since October 1999, maintenance chemotherapy consisting of oral 6 mercaptopurine 9 mg/m2 daily, methotrexate 15 mg/m2 weekly and ATRA 45 mg/m2 for 2 weeks every three months was added. Complete remission rates and duration, relapse rate and toxicity were studied. RESULTS: 22 of 24 evaluable patients (91.6%) achieved CR. The median duration of remission was 13 months (range 2-55 months). Three patients (12.5%) relapsed. Two patients (8.3%) developed retinoic acid syndrome and responded to dexamethasone. Five patients (20.8%) died one each of refractory disease, during remission induction and of relapse. Two patients died while in remission. CONCLUSION: ATRA and combination chemotherapy results in high complete remission rates and low relapse rate in newly diagnosed APL. Maintenance therapy may be useful in preventing relapses.     

Hospitalization Risk According to Geriatric Assessment and Laboratory Parameters in Elderly Hematologic Cancer Patients

Background: Utilizing geriatric screening tools for the identification of vulnerable older patients with canceris important. The aim of this study is to evaluate the hospitalization risk of elderly hematologic cancer patientsbased on geriatric assessment and laboratory parameters. Materials and Methods: In this cross sectional study61 patients with hematologic malignancies, age 65 years and older, were assessed at a hematology outpatientclinic. Standard geriatric screening tests; activities of daily living (ADL), instrumental activities of daily living(IADL), Mini Nutritional Assessment (MNA), Mini Mental State Examination (MMSE), timed up and go test(TUG), geriatrics depression scale (GDS) were administered. Demographic and medical data were obtained frompatient medical records. The number of hospitalizations in the following six months was then recorded to allowanalysis of associations with geriatric assessment tools and laboratory parameters. Results: The median age of thepatients, 37 being males, was 66 years. Positive TUG test and declined ADL was found as significant risk factorsfor hospitalization (p=0.028 and p=0.015 respectively). Correlations of hospitalization with thrombocytopenia,vitamin B12 and folic acid deficiency were statistically significant (p=0.004, p=0.011 and p=0.05 respectively).Conclusions: In this study, geriatric conditions which are usually unrecognized in a regular oncology office visitwere identified. Our study indicates TUG and ADL might be use as predictive tests for hospitalization in elderlyoncology populations. Also thrombocytopenia, and vitamin B12 and folic acid deficiencies are among the riskfactors for hospitalization. The importance of vitamin B12 and folic acid vitamin replacement should not beunderestimated in this population.     

Use of arsenic trioxide (As2O3) in the treatment of patients with acute promyelocytic leukemia: the M. D. Anderson experience

BACKGROUND: Approximately 20-30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) and an anthracycline develop recurrent disease. It has been reported that arsenic trioxide (As(2)O(3)) is effective in this setting. The authors report the experience of The M. D. Anderson Cancer Center with As(2)O(3) in the treatment of patients with recurrent APL. METHODS: Twelve patients who developed recurrent APL after treatment with ATRA were included. Patients received intravenous As(2)O(3) 0.15 mg/kg per day until they achieved a complete remission (CR) or up to a maximum of 60 days. Their median age was 44 years (range, 26-72 years), and the median duration of first remission was 52 weeks (range, 23-292 weeks). RESULTS: All 12 patients achieved a CR. The median time to achieve CR was 52 days (range, 27-75 days). Seven of 10 evaluable patients achieved a molecular remission (i.e., polymerase chain reaction [PCR] analysis was negative for the gene encoding fusion of the nuclear receptor for retinoic acid to the PML gene at the time of CR; 70% of patients; 95% confidence interval, 0.35-0.93), and all other patients had negative PCR results after they received post-remission therapy. All patients received subsequent therapy: Four patients received As(2)O(3) alone, six patients received As(2)O(3) with other chemotherapeutic agents, and two patients received idarubicin plus ATRA without As(2)O(3). Eight patients continued in CR after a median follow-up of 24 months (range, 9-45 months). Side effects were mild, except for two patients who developed Grade 2 and 3 peripheral neuropathy, respectively; one of those patients required discontinuation of therapy. CONCLUSIONS: As(2)O(3) is effective and well tolerated therapy for patients with recurrent APL. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable.     

Treatment of newly-diagnosed acute promyelocytic leukemia with liposomal all-trans retinoic acid.

It has been postulated that recurrence of disease in some patients with newly-diagnosed APL induced into CR, and subsequently maintained, with single agent oral ATRA results from the decline in ATRA levels that occurs with repeated dosing. Administration of liposomal ATRA (lipoATRA) circumvents, for perhaps several months, the decrease in ATRA levels and produces CRs in patients with relapsed APL. These findings led us to administer lipoATRA "monotherapy" to patients with newly-diagnosed APL. Patients received lipoATRA (90 mg/m2) for induction and continued to receive the drug, by itself, for 9 months unless 2 PCR tests done within 2-4 weeks of each other at a sensitivity level of 10(-4) were positive at 3 or 6 months from CR date, in which case idarubicin was added to lipoATRA. If the PCR test was negative 9 months from CR date, treatment stopped. 34 patients were enrolled, of whom 79% entered CR. The PCR test at time of CR was positive in 23/24 patients, but was negative in 24/26 (92%) 3 months later. Of most interest 11 of the 26 evaluable responding patients have remained PCR negative (tested Q 3 months) with a median follow-up of 18 months (range up to 34 months). It is generally believed that this type of result would be unlikely with oral ATRA monotherapy. Recurrence of morphologic APL has occurred in 4 patients, at 5, 6, 12, and 12 months, with a median follow-up time of 18 months in the patients remaining alive in CR. Comparison of this lipoATRA +/- idarubicin trial with oral ATRA + idarubicin induction and idarubicin + POMP maintenance, our previous trial, indicates similar survival, CR, and DFS in CR rates, with a suggestion that lipoATRA may produce lower CR rates and hence shorter survival in patients with high-risk disease (wbc count > 10,000/microliter. Nonetheless, the rates and duration of PCR negativity produced by lipoATRA monotherapy suggest that lipoATRA is a superior anti-APL agent than oral ATRA.     

Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy.

PURPOSE: To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both. RESULTS: Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ months, six remained in second CR after 17+ to 66+ months, and three patients had died. The 5-year event-free survival (EFS), relapse, and overall survival rates were 71%, 27%, and 90%, respectively. No difference between adults and children included in the APL93 trial was seen for CR rate, 5-year relapse rate, EFS, and overall survival, but significantly better survival was seen in children after adjustment on WBC counts (P =.02) and incidence of microgranular M3 variant (P =.04). CONCLUSION: ATRA combined with CT for induction and also probably for maintenance provides as favorable results in children with APL as in adults and currently constitutes the reference first-line treatment in both age groups.     

Effect of vitamin B12, folate, and dietary supplements on breast carcinoma chemotherapy--induced mucositis and neutropenia

BACKGROUND: Although patients with malignant disease frequently use dietary supplements, the effects of these agents with regard to chemotherapy are unclear. Therefore, the authors investigated the influence of vitamin B12, folate, and nutritional supplements on chemotherapy-induced toxicity. METHODS: Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts. Toxicity was evaluated by measuring absolute neutrophil counts and the frequency and severity of oral mucositis. RESULTS: Of the 49 women who submitted questionnaires, 35 (71%) took a combined total of 165 supplements. Compared with patients in a previous study (performed in 1990), patients in the current study had dramatically increased serum folate levels. Initial neutrophil count, but not type of chemotherapy, patient age, or serum vitamin B12 level, was predictive of nadir absolute neutropenia and the decrease from initial neutrophil count to nadir (Nfall). After adjusting for initial neutrophil count, Nfall was found to be lower for women who were taking supplements compared with women who were not taking supplements (P = 0.01) and for women who were taking multivitamins (P = 0.01) or vitamin E (P = 0.03). Women with serum folic acid levels < 20 ng/mL had a smaller decrease in neutrophil count after chemotherapy than did women with higher folate levels (P = 0.04). No significant association between oral mucositis and initial neutrophil count, nadir neutrophil count, Nfall, age, vitamin B12 level, or folate level was found. CONCLUSIONS: The decrease in neutrophil count caused by chemotherapy was ameliorated by dietary supplementation with a multivitamin or vitamin E. In contrast, high serum folate levels were associated with the exacerbation of this decrease in neutrophil count.     

以亚砷酸为主方案治疗急性早幼粒细胞白血病的分子生物学疗效

 目的　观察以亚砷酸为主的方案治疗初治的急性早幼粒细胞白血病（APL）的细胞学及分子生物学疗效。方法　56例APL患者均经骨髓细胞形态学检查、组织化学检查、免疫表型测定以及FISH法和实时定量PCR法检测PML／RARα融合基因而确诊。诱导化疗方案采用亚砷酸10 mg／d,静脉滴注,直至获得完全缓解。缓解后采用亚砷酸与化疗交替治疗,以亚砷酸为主。对20例患者的PML／RARα融合基因进行动态观察。结果　56例PML-RARα融合基因阳性的初治APL患者完全缓解率98.2 ％,CR中位时间32（23～42） d。实时定量RT-PCR检测阳性的32例患者中位随访期3年,总生存率100 ％,复发率3.12 ％。完全缓解24个月后分子生物学缓解率100 ％（6／6）。结论　以亚砷酸为主的方案治疗PML／RARα融合基因阳性的APL患者疗效好,血液学缓解后24个月有可能获得分子生物学缓解。     

Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men

Deficient levels of folic acid and vitamin B12 are associated with elevated chromosome damage rate and high concentrations of homocysteine in the blood. We have therefore performed a study to determine the prevalence of folate deficiency, vitamin B12 deficiency and hyperhomocysteinemia in 64 healthy men aged between 50 and 70 years, and evaluate the relationship of these micronutrient levels in the blood with the micronucleus frequency in peripheral blood lymphocytes. We also performed a placebo-controlled, double-blind intervention study to determine whether supplementation of the diet with a daily dose of 0.7 mg (as a supplement in cereal) or 2.0 mg (in a tablet) over a period of 4 months resulted in a significant alteration of folate status, homocysteine status and the micronucleus index. Twenty-three per cent of the men were serum folate deficient (<6.8 nmol/l), 16% were red blood cell folate deficient (<317 nmol/l), 4.7% were vitamin B12 deficient (<150 pmol/l) and 37% has plasma homocysteine levels >10 micromol/l. In total, 56% of the men had one or more abnormal blood values for folate, vitamin B12 or homocysteine. The micronucleus index of these men (n = 34) in cytokinesis-blocked binucleated cells (19.2 +/- 1.1) was significantly elevated (P = 0.02) when compared to the micronucleus index of the rest of the men who had normal levels of folate, vitamin B12 and homocysteine (16.3 +/- 1.3, n = 30). Interestingly, the micronucleus index in men with normal folate and vitamin B12, but homocysteine levels >10 micromol/l (19.4 +/- 1.7, n = 15) was also significantly higher (P = 0.05) when compared to those with normal folate, vitamin B12 and homocysteine. This novel result was also supported by the observation that the micronucleus index and plasma homocysteine were significantly (P = 0.0086) and positively correlated (r2 = 0.172) in those subjects who were not deficient in folate or vitamin B12. The micronucleus index was not significantly correlated with folate indices, but there was a significant (P = 0.013) negative correlation with serum vitamin B12 (r2 = 0.099). Daily supplementation of the diet with 0.7 mg free folic acid in cereal for 2 months followed by 2.0 mg free folic acid via a tablet produced a 4- fold increase in plasma folate, a 2.6-fold increase in red blood cell folate and a 11% reduction in plasma homocysteine; however, these changes were not accompanied by a reduction in the micronucleus index. In conclusion, it is apparent that elevated homocysteine status, in the absence of vitamin deficiency and low, but not deficient, vitamin B12 status are important risk factors for increased chromosome damage in lymphocytes.