The management of acute myelogenous leukemia in the elderly: ten-year experience in 118 patients.

This retrospective study was undertaken to analyse the survival pattern of 118 consecutive, unselected patients with acute myelogenous leukemia (AML) aged between 60 and 82 years observed at a single centre over a 10-year period (1981-1991). Thirty-two per cent of cases had an antecedent hematological disorder (AHD), and 7 per cent had a secondary AML. Forty patients (39 per cent) were managed with palliative intent with short courses with oral hydroxyurea +/- 6-thioguanine. In contrast to 78 patients (61 per cent) selected for remission-induction treatment, these were significantly older (P < 0.0001), had a greater incidence of AHD (P < 0.039) and of hypoplastic AML (P < 0.017), and an inferior amount of blast cells in the bone marrow (P < 0.003). Patients undergoing remission-induction chemotherapy were managed with DAT-like chemotherapy, high-dose cytosine arabinoside (HD-ara-C), and mitoxantrone-based regimens. The complete response (CR) rate was 29 per cent. Response was higher with the two most intensive HD-araC and mitoxantrone-etoposide-araC programmes (P < 0.026), and correlated favourably with no AHD (P < 0.04) and lower blast cell count in the peripheral blood (P < 0.02). Overall survival of responders was longer than in palliation and nonresponder groups (P < 0.025 and P < 0.001, respectively). In the active treatment group, survival correlated with performance status (P < 0.005) and blast cell count (P < 0.05). Infection was the main cause of morbidity during active treatment, accounting for most induction failures (60 per cent), followed by haemorrhage (12 per cent) and resistant disease (12 per cent). These results from an unselected series represent an improvement over those obtained by us in previous years (1971-1980), and show that intensive treatment programmes are applicable to the elderly with AML and that prolonged disease-free survival is possible for some. Improving further CR rate and duration will depend equally on the optimization of supportive care measures and the introduction of more effective therapeutic modalities.     

Short-term remission induction and consolidation therapy for adult acute myelogenous leukemia

One hundred and ninety two adults (median age 44 years) with de novo or secondary (n = 17) acute myelogenous leukemia (AML) were managed with a maximum of six intended courses with adriamycin 25 mg/m2/d for three days, plus cytarabine 200 mg/m2/d and 6-thioguanine 200 mg/m2/d for seven days (short-term therapy, STT). Twenty eight patients not in remission after the first course were given cytarabine 2 g/m2/bd for six days, a treatment that was highly toxic and gave a low CR rate. One hundred and twenty-six patients overall (66 per cent) achieved a complete remission (CR), 117/164 (71 per cent) after one to three standard courses (median 1), and 9/28 (32 per cent) after high-dose cytarabine. Median CR duration was 12 months. By multivariate analysis, younger age, blast count less than or equal to 50 x 10(9)/L, and de novo AML were associated with a better outcome (p less than 0.05). CR duration correlated favourably with FAB M3 morphology and total number (five or six) of cycles (p less than 0.05). In patients receiving five or six total courses, median CR length resulted 15.5 months and leukemia-free survival at 3 years 37 per cent. Therapy was curtailed in one fourth of CR patients because of unacceptable toxicity, and there were nine early deaths attributable to therapy-related complications among 126 CR cases. STT may be a worthwhile form of treatment for patients with de novo non-hyperleukocytic AML that are able to tolerate five or six consecutive induction-like chemotherapy courses.     

Acute myeloid leukemia in the elderly: results of an individualized approach in two centres

We retrospectively assessed seventy-four consecutive patients with AML over 65 years of age (median 71; range 65-88) treated with an individualized approach in two specialized cancer centers. Patients were managed according to their performance status (PS) and associated diseases in both institutions. The proportion of patients with poor PS (3-4) was higher in center 1 (37%) than in center 2 (10%) and in center 1 palliative treatment was given more frequently (16/32 patients) than in center 2 (7/42 patients). Fifty-one patients received intensive combination chemotherapy including an anthracycline and ara-C or VP16 (2 patients) and 36 patients received a second intensive course as reinduction or as consolidation treatment after complete remission. Patients not eligible for myelosuppressive chemotherapy were treated with palliative measures (23 patients). With intensive chemotherapy, complete remission (CR) was achieved in 29 of 51 patients (57%), after first (20 patients) or second course (9 patients) and the rate of deaths during induction was 14% (7 patients). The CR rate was lower for patients with performance status >or= 2 (48%) as compared to patients with performance status or= 2) was associated with reduced survival (hazard ratio: 3.29, 95% confidence interval: 1.75-6.17). Overall 2-years and 5-years survival were 20% and 11% for the patients treated intensively. From this study it appears that an individualized approach of treatment with intensive chemotherapy for selected patients offers a substantial CR rate and an improvement in survival. This analysis also suggests that differences in outcome between single institutions can be explained mainly by referral and selection biases     

77例老年急性髓性白血病患者的预后因素分析

背景与目的:老年急性髓性白血病(acutemyelogenousleukemia,AML)有独特的生物学及临床特征,患者对治疗的反应差、生存期短。本研究旨在探讨老年AML的预后因素。方法:对上海市第一人民医院1994～2005年收治的77例老年AML患者可能影响预后的因素进行Kaplan-Meier生存分析,然后对有意义的因素进行Cox比例风险模型分析。结果:可评价患者72例。年龄60～70岁者中位生存期(350天)显著长于年龄>70岁者(60天)(P<0.001),CR率显著提高(71.4%vs.29.4%,P=0.001);生存状态(performancestatus,PS)0或1分者中位生存期(402天)显著长于2、3、4分者(31天)(P<0.001),CR率显著提高(75.0%vs.15.0%,P<0.001);原发者中位生存期(98天)显著长于继发者(32天)(P=0.007),CR率显著提高(50.0%vs.0%,P=0.023);使用亚标准剂量的蒽环类药物者中位生存期(293天)显著长于减量使用者(35天)(P=0.006),CR率显著提高(63.6%vs.33.3%,P=0.02)。骨髓原始细胞(bonemarrowblastcell,BMblast)比率≤50%者中位生存期(98天)显著长于>50%者(55天)(P=0.006);预后良好核型者中位生存期(293天)显著长于预后不良或正常核型者(31天)(P=0.005);CD34阴性者中位生存期(201天)显著长于阳性者(36天)(P<0.001)。外周血白细胞数量(peripheralbloodwhitebloodcellcount,PBWBC)大于10×109/L者CR率(50.0%)显著高于PBWBC小于10×109/L者(25.0%)(P=0.043);化疗者CR率(50.0%)显著高于支持治疗者(0%)(P=0.001)。Cox比例风险模型分析显示影响生存期的7个因素均具有独立性和统计学意义。结论:年龄>70岁、PS为2～4分、骨髓原始细胞比率>50%、继发性、不良核型、CD34 以及蒽环类药物剂量强度是影响患者生存期的主要预后因素,蒽环类药物剂量显著影响CR率。     

Intensive retreatment of adults and children with acute lymphoblastic leukemia.

Twenty-three patients (16 adults) failing their first or subsequent (n = 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four-drug induction phase is followed by early consolidation with teniposide-cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide-cytarabine with vincristine-cyclophosphamide, and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3-11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p less than 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation.     

High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia

In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables.     

Long-term results of the HEAVD protocol for adult acute lymphoblastic leukaemia

Between 1979 and 1987, 82 adults (age 14–71 years) with acute lymphoblastic leukaemia (ALL) were treated with a 6-course protocol called HEAVD, the main feature of which was the early postremission administration of escalating doses of doxorubicin (total 405 mg/m²) and cyclophosphamide (total 2.5 g/m²). A complete remission (CR) was attained in 66 patients (80%, 95% confidence intervals, [CI] 71%–89%). Factors affecting favourable CR achievement were age < 60 years and absence of lymphadenopathy-hepatosplenomegaly at presentation (P < 0.05). Median duration of CR was 27 months. 26 patients remain in first continuous and unmaintained CR, 18 of whom between 5.9 and 11.1 years, for an estimated 39% prolonged disease-free survival (95% CI 27%–51%). CR duration correlated significantly with absolute blast cell count (15 × 10⁹/l or less compared to more) and age (30 years or under compared to over). Overall, 29 patients are alive with a median follow-up of 6.7 years, the projected long term survival being 35% at 11 years (95% CI 24%–46%). Treatment-related toxicity included 1 lethal case of L-asparaginase-related thromboembolism and 3 toxic deaths among 66 CR patients. Late-onset toxicity was not observed in long-term survivors. The relatively late occurrence of endpoint events (relapse and death) in adult ALL confirms that long-term updating is necessary to determine the curative potential of modern chemotherapy programs for the disease.     

Treatment of acute myeloid leukemia in the elderly: a clinical dilemma

Fifty-four patients representing all the cases of acute myeloid leukemia in patients aged over 60 years, presenting to three adjacent hospitals, were studied. Only 26 of the 54 patients were considered suitable for remission induction with intensive combination chemotherapy which produced seven complete remissions (CR) (26 per cent). Eighteen of the 54 patients survived longer than three months--11 of these had received remission induction chemotherapy (five CRs), two low dose cytarabine, one vincristine and vitamin A and four supportive treatment alone. By six months all the patients who had received supportive treatment had died. Patients who received intensive chemotherapy spent 77 per cent of the first 90 days in hospital and half died in hospital. Patients receiving differentiating agents or supportive care spent more time at home (37 per cent, 34 per cent of the first 90 days, respectively) but had shorter overall survival. Assessment of clinical characteristics in an attempt to predict response to treatment and survival indicated that poor performance status and the presence of infection were the most important factors. Analysis was limited by the statistically small number in the group. At present there is no reliable method of predicting which patients will respond well to treatment with intensive chemotherapy. The clinical dilemma is whether to treat more intensively to benefit a minority, or to use supportive treatment to allow more time to be spent at home albeit with a shorter overall survival.     

Short-term therapy for acute myelogenous leukemia

Since 1978, 187 patients (age range, 15 to 59, median 44 years) have received short-term chemotherapy as part of three sequential open studies (B-IX, X, Xb) or a randomized clinical trial (B-XI). An intended six cycles of Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), cytarabine (ara-C), and thioguanine (TG) were administered with as short an intercycle time as possible. No further therapy was administered. Complete remission (CR) was achieved in 118 of 187 patients (63%). On univariate and multivariate analyses achievement of CR correlated adversely with a low serum albumin at presentation and an antecedent marrow disorder. Forty-five patients continue in first remission between 15 months and 8 1/2 years, no relapses being seen after 3 1/2 years (median follow-up, 3 1/2 years). The median duration of remission was 1 year. M3 morphology, a blast count less than 100 x 10(9)/L, and absence of hepatosplenomegaly correlated favorably with remission duration. There was no difference in duration of remission between patients receiving 3, 4, 5, or 6 cycles. The best results overall were achieved in patients under the age of 40, with 43% projected to remain free of disease at 5 years. Fifty patients remain alive between 17 months and 9 years, the predicted actuarial survival being 25% at 5 years.     

Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia: Cancer and Leukemia Group B study 9420.

PURPOSE: The purpose of the study is to investigate the tolerability of interleukin 2 (IL-2) after intensive chemotherapy in elderly acute myeloid leukemia (AML) patients in first complete remission (CR). EXPERIMENTAL DESIGN: AML patients > or =60 years in CR after induction and consolidation chemotherapy on Cancer and Leukemia Group B study 9420 were eligible if they had neutrophils > or =1 x 10(9)/liters and platelets > or =75 x 10(9)/liters. Patients received low-dose IL-2 (1 x 10(6) IU/m(2)/day s.c. for 90 days) or low-dose IL-2 with intermediate pulse doses (6-12 x 10(6) IU/m(2)/day s.c. for 3 days) every 14 days (maximum five pulses). In a subset of patients, we investigated the expression of NKG2D ligands by leukemic cells because they are likely important mediators of natural killer cytotoxicity. RESULTS: Of 35 CR patients receiving IL-2, 34 were evaluable for toxicity. Median age was 67 (range, 60-76) years. Thirteen of 16 patients receiving low-dose IL-2 completed the planned therapy, and 11 of 18 who also received intermediate pulse dose IL-2 therapy completed all five pulses. The spectrum of toxicity in both groups was similar, with predominantly grade 1-2 fatigue, fever, injection site reactions, nausea, anemia, and thrombocytopenia. Grade 3-4 hematological and nonhematological toxicity were more frequent in patients also receiving intermediate pulse dose IL-2 therapy. Grade 3-4 fatigue and hematological toxicity, although uncommon, were the major causes for discontinuing or attenuating therapy. In 8 cases, mRNA for one or more NKG2D ligands was detected in leukemic cells obtained at diagnosis before treatment. CONCLUSIONS: Low-dose IL-2, with or without intermediate pulse dose therapy, given immediately after chemotherapy in first CR to elderly AML patients is well tolerated. Expression of NKG2D ligands by leukemic cells was detected in the majority of cases tested and should be assessed for correlation with response to IL-2 in future studies.     

The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia

BACKGROUND: Valproic acid (VPA) inhibits histone deacetylase activity and, synergizing with all-trans retinoic acid (ATRA), achieves differentiation induction of myeloid blast cells in vitro. METHODS: We used VPA in 58 patients with acute myeloid leukemia (AML) who were too old and/or medically unfit to receive intensive chemotherapy (32 AML secondary to myelodysplastic syndrome [MDS], 22 de novo AML, 4 AML secondary to myeloproliferative syndrome). VPA serum concentrations were 50-100 mug/mL. Thirty-one patients received VPA monotherapy. ATRA was added later in 13 patients who did not respond or who relapsed. Another 27 patients received VPA plus ATRA from the start. Median treatment duration was 93 days for VPA and 88 days for ATRA. RESULTS: The response rate was only 5% according to International Working Group (IWG) criteria for AML but was 16% when IWG response criteria for MDS were used, which capture hematologic improvement and stabilization of the disease. These endpoints, which are not necessarily correlated with diminishing blast counts, are relevant for the patients' quality of life. Among 23 patients with a peripheral blast count > 5%, 6 (26%) showed a diminishing blast count, and 5 of these had a complete peripheral blast clearance. CONCLUSIONS: Future trials should combine VPA with chemotherapy or demethylating agents.     

Inv(16) may be one of the only ‘favorable’ factors in acute myeloid leukemia: A report on 19 cases with prolonged follow-up

We report our experience of treatment of acute myeloid leukemia (AML) with inv(16). Nineteen of 531 (3.6%) cases of newly diagnosed AML karyotyped over a 12 year period had inv(16)(p13q22) and none had t(16;16) or del 16q. Morphologically, all patients had M_4eo. All patients were treated with conventional anthracycline—Ara-C chemotherapy, followed by moderate or more intensive consolidation chemotherapy. All patients received central nervous system (CNS) prophylaxis with intrathecal methotrexate and Ara-C, and cranial irradiation.

Eighteen patients (95%) achieved complete remission (CR). Three had a bone marrow relapse, one had a CNS relapse and 14 patients remained in first CR, 11 of them with a followup greater than 44 months. Disease-free survival was 74% after 10 months, and actuarial survival 88% after 4 years, and 62% after 6 years. No other AML subgroup, in our experience, had a long-term survival approaching that of AML with inv(16) (although similar favorable outcome may be anticipated in acute promyelocytic leukemia treated by a combination of retinoic acid and chemotherapy).     

Adolescent and adult lymphoblastic leukaemia: prognostic factors and response to treatment

Thirty consecutive patients with acute lymphoblastic leukaemia (ALL) who received treatment at Christchurch Hospital between 1972 and 1982 were reviewed. Complete remission (CR) was achieved in 80 per cent with a median survival of 65 weeks. Eleven of 30 patients had one or more of the following features--B cell ALL, a mediastinal mass, the Philadelphia chromosome (Ph1) and age 60 years or older at diagnosis. Although CR was obtained in 8 of these patients none survived three years. The remaining 19 patients were regarded as 'good risk' and treated by moderate intensity chemotherapy schedules. CR was obtained in 16 of these patients (84 per cent) and the estimated 5 year survival was 62 per cent with 6 patients remaining in remission from 5 to 9 years from diagnosis. These results demonstrate the value of objective and reproducible clinical and laboratory findings in defining a subset of ALL patients which may not require high intensity chemotherapy schedules.     

Acute myelogenous leukemia in elderly patients not eligible for intensive chemotherapy: the dark side of the moon.

BACKGROUND: Acute Myelogenous Leukemia (AML) is a common disease in people aged>60 years. About 50% of the patients are not eligible for aggressive chemotherapy (CT) and are only managed with conservative approaches. Results in this subset of patients have not been reported so far. PATIENTS AND METHODS: We retrospectively evaluated 244 consecutive elderly AML patients (M/F 143/101, median age 72 years, range 60-90) diagnosed at our institution from January 1989 to December 1998 and not eligible for intensive CT. Eighty-nine patients (36.5%) had evolved from previous myelodysplasia (sAML). Fifty-three out of 192 (26.4%) patients with available bone marrow (BM) analysis had oligoblastic leukaemia (blasts<40% and WBC<15x10(9)/l). RESULTS: Sixty-seven patients (27.5%) were managed with supportive treatment only. One hundred seventy-seven patients (72.5%), in order to control disease, received conservative CT, consisting of Hydroxyurea (HU) (127 patients, 71.7%), Cytarabine and 6-Thioguanine (39 patients, 22%) or low-dose cytarabine (11 patients, 6.3%). Median overall survival was 179 days (1-3278) with 50 patients (20.5%) surviving>12 months. Older age (>75 years), poor WHO PS (>2), lower PLT levels (<50x10(9)/l) and higher absolute peripheral blast count (>5x10(9)/l) showed a negative prognostic impact on survival in multivariate analysis. CONCLUSIONS: Our data outline the great heterogeneity of elderly AML patients not eligible for intensive CT. A simple scoring system including easily evaluable parameters, which could distinguish subjects with different prognosis, is proposed. Moreover, randomized studies in order to establish best conservative approaches are warranted.     

ChlVPP combination chemotherapy for Hodgkin's disease: long-term results

Two hundred and eighty-four patients with advanced Hodgkin's disease (HD) (stage II with poor prognostic features and stage III/IV) have been treated with the ChlVPP combination chemotherapy regimen (chlorambucil, vinblastine, procarbazine and prednisolone) in a single-centre unselected series. Median follow up is 92 months. Fifty-five patients had previously received radiotherapy but none had received previous chemotherapy. Eighty-five per cent of previously untreated patients and 91% of previously irradiated patients entered complete remission (CR); 71% and 68% of these respectively remain in CR at 10 years and 65% and 64% of each group respectively are alive at 10 years. On univariate analysis, age, stage, site of visceral disease and lymphocyte count predicted survival and on multivariate analysis age, absence of symptoms, absence of lung, liver or bone marrow disease and achieving a CR remained important predictors of survival. Acute toxicity was mild. The 10 year actuarial risk of acute leukaemia was 2.7%. This study adds further support to the view that chlorambucil is as effective and less toxic than mustine in combination chemotherapy for HD. We suggest that MOPP chemotherapy is no longer routinely indicated for HD.     

Long-term survival in patients with human immunodeficiency virus-associated small non-cleaved cell lymphoma: the role for short course intensive chemotherapy

While intensive chemotherapy is recommended for the treatment of non-HIV related adult small non-cleaved lymphoma (SNCL), including Burkitt's and Burkitt-like lymphoma, optimal treatment for patients with HIV-associated SNCL is not known. We assessed remissions and survival in a cohort of 44 consecutive HIV positive patients diagnosed with SNCL at our hospital between June 2000 and November 2001 using chart and pathology data. Median follow-up, survival and survival at the median follow-up time were 4.5 months, 4 months and 49% respectively. Of this cohort 39% were complete responders (CR) and 36% were long-term lymphoma-free survivors. Two patients relapsed from CR. Short course intensive chemotherapy (McMaster) was administered to 23 patients; 17 received less intensive conventional combination chemotherapy; and four received single-agent chemotherapy or no treatment. In the McMaster group, 38% (9/23) achieved CR with no relapses. Seven patients (30%) died of toxicity compared with one (6%) in the less intensively treated group. Of the stage I patients, 75% (6/8) achieved long-term CR with half being treated conventionally. Conventional chemotherapy may be curative for early stage HIV-SNCL. In advanced disease, McMaster chemotherapy was found to be associated with substantial early mortality but was curative in a significant number of patients.     

Integrating geriatric assessment and genetic profiling to personalize therapy selection in older adults with acute myeloid leukemia

IntroductionSurvival benefit associated with intensive over low-intensity chemotherapy in older adults with acute myeloid leukemia (AML) is controversial. Geriatric assessment and genetic risk categories correlate with survival following intensive chemotherapy in older adults with AML and can guide treatment selection.Materials and methodsIn a single-center trial, we integrated both geriatric assessment, and genetic risk categories to personalize selection of intensive versus low-intensity chemotherapy in older adults ≥60 years with AML (NCT03226418). In the present report, we demonstrate feasibility of this approach.ResultsBroad eligibility criteria and co-management of patients with community oncologists allowed enrollment of 45% of all patients with AML treated at our center during the study period. The median time from enrollment to therapy initiation was two days (range 0–9). Over half of the trial patients had a score of ≥3 on hematopoietic cell transplantation comorbidity index, impairment in physical function (Short Physical Performance Battery), and Montreal Cognitive Assessment. Three fit patients received intensive chemotherapy, whereas other patients received low-intensity chemotherapy. Mortality at 30 days from diagnosis was 3.7% (95% confidence interval [CI] 0.7–18.3%) and at 90 days was 29.6% (95% CI 15.9–48.5%). One-year overall survival was 66% (95% CI 60–87%).DiscussionOur data demonstrate the feasibility of integrating geriatric assessment in precision oncology trials to define fitness for intensive chemotherapy. Broad eligibility criteria and academic-community collaboration can expand access to clinical trials.     

TE T2基因阳性急性髓细胞白血病38例分析

目的：分析TET2基因阳性急性髓细胞白血病（AML）患者的临床及实验室特点,探讨可能影响治疗效果的因素。方法：收集38例TET2基因突变阳性AML患者的临床及实验室资料,并回顾性分析其中可能影响治疗效果的因素,TET2基因检测采用实时定量PCR方法。结果：38例患者中21例接受化疗,获得完全缓解（CR）12例（57．14％）,未缓解（NR）5例（23．81％）,疾病进展（PD）4例（19．05％）。应用不同化疗方案治疗后缓解率不同,应用去甲基化治疗的4例第一个疗程治疗后均达到完全缓解,未应用去甲基化治疗的17例中CR 8例（47．06％）、NR 5例（29．41％）、PD 4例（23．53％）。白血病细胞免疫表型CD34阴性、CD13阴性、CD33阳性者化疗后CR率更高,差异具有统计学意义（P＜0．05）。TET2基因阳性AML患者的CR率与年龄、性别、发病时白细胞计数、血红蛋白、血小板计数、白血病细胞免疫表型（CD56、CD9、HLA－DR）、是否伴有其他预后基因及复杂染色体核型无明显相关性。结论：TET2基因阳性AML患者的CR率与化疗方案及白血病细胞免疫表型CD34、CD13及CD33相关。去甲基化治疗可提高TET2基因阳性AML患者的CR率。影响TET2基因阳性AML患者疗效及长期生存的因素尚需进一步探讨。     

Management of advanced stage intermediate grade non-Hodgkin's lymphomas.

The treatment result of 271 cases of advanced stage intermediate grade lymphoma were reviewed. Ninety-four patients received CHOP chemotherapy, 45 BACOP and 17 m-BACOD. The clinical characteristics of the three groups of patients were comparable. Patients receiving CHOP had a complete response (CR) rate of 60 per cent, the disease-free survival of CR patients was 31 per cent at 5 years. The overall survival following CHOP chemotherapy was 38 per cent at 5 years. The use of the BACOP or m-BACOD regime did not appear to improve significantly the prognosis of these patients. Clinical staging, B symptoms, age and serum lactate dehydrogenase level were the most important independent prognostic factors.     

Factors affecting remission and survival in patients with advanced Hodgkin's disease treated with MVPP

One hundred and fourteen patients with clinical or pathological stages IIIB and IV Hodgkin's disease have been treated with MVPP chemotherapy followed by radiotherapy to sites of previously bulky disease. The minimum follow-up is 2 years with a median of 5 years. The overall remission rate was 92 per cent with 74 per cent achieving CR. A discriminant analysis showed that the presence of bulky disease was the only independent factor that predicted a lower chance of CR (66 per cent vs 82 per cent, P = 0.045). The 5-year survival was 70 per cent overall and 85 per cent for CR patients. A Cox multivariate analysis demonstrated that stage III disease, age less than 36 years and female sex were all variables which independently predicted a more favourable prognosis in terms of overall survival. However, a similar analysis for survival of CR patients showed that age less than 36 years and the absence of bulky disease were the only two factors to independently predict a more favourable outcome. Of 14 patients who did not receive the chemotherapy according to protocol 5 have relapsed compared to 7 of 70 who did. A Cox analysis confirmed that this variable was the only one of significant prognostic import in predicting relapse-free survival. Using the Cox analyses we have been able to devise a scoring system which accurately predicts the outcome for these patients. This model may be useful in determining which patients have a worse prognosis following treatment with MVPP thus allowing more intensive therapy to be given to such patients while minimising treatment for those with favourable features.