Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases

To define better the risk of epipodophyllotoxin-related acute myeloid leukemia (AML) after extended follow-up and to assess responses to intensive salvage therapy, all patients who developed this complication after treatment for acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) in consecutive clinical trials at St Jude Children's Research Hospital from 1979 to 1994 were studied. Cases with 'lineage switch' or 'clonal selection' were excluded. Epipodophyllotoxin-related AML developed in 32 of 1140 patients treated for ALL and in three of 332 treated for NHL; it was a first adverse event in 25 and two cases, respectively. The complication was diagnosed at 12-130 months (median 34 months) after the initiation of treatment with epipodophyllotoxins; all but one of the cases occurred within 73 months, indicating that the risk is negligible after 6 years. The predominant karyotypic feature was 11q23 translocations (71% of cases); 21q22 rearrangements were rare. In a stepwise Cox regression analysis, two factors increased the risk of this complication: weekly or twice weekly administration of epipodophyllotoxins (P < 0.001); and the administration of asparaginase immediately before epipodophyllotoxin therapy (P < 0.001). Initial responses to salvage therapy were comparable to those reported for de novo AML: 92% of the evaluable patients entered complete remission after combination treatment. Single-agent therapy with 2-chlorodeoxyadenosine induced complete or partial remissions in one-half of the patients treated. The long-term survival rate was dismal. Of the 17 evaluable patients treated exclusively with chemotherapy, only one is alive at 84 months, compared to three of 16 patients who underwent bone marrow transplantation (alive at 10, 23 and 73 months). Cases of epipodophyllotoxin-related AML constitute a unique clinical syndrome that will require innovative strategies for cure.     

乙酰肝素酶Arg307Lys多态性与成年人急性白血病发病风险的关系

目的 探讨乙酰肝素酶( HPSE) Arg307Lys多态性与成年人急性白血病发病风险的关系。方法按照1:1配对病例对照研究方法,选择中国北方地区100例急性髓系白血病(AML)和25例急性淋巴细胞白血病(ALL)患者为病例组,100名中国北方地区健康人为对照组,采用聚合酶链反应-限制性片段长度多态性( PCR-RFLP)方法检测观察对象外周血HPSE Arg307Lys基因多态性。结果成年ALL病例组和对照组Lys/Lys、Arg/Lys、Arg/Arg基因型分布频率分别为80％、16％、4％和75％、23％、2％,两组比较差异无统计学意义(x2= 0.07,P= 0.79; x2= 0,08,P= 0.78)。AML病例组Lys/Lys、Arg/Lys、Arg/Arg基因型频率分别为85％、14％、1％,与对照组比较差异无统计学意义(x2=3.03,P=0.08;x2=3.15,P=0.08)。携带HPSE Arg307Lys突变基因(AA/AA+AG)的个体不增加AML及ALL的发病风险(AML:x2= 3.13,P=0.07,OR= 1.89,95％CI 0.93～3.83;AL：x 2=0.27,P=0.60,OR= 1.33,95 ％CI 0.45～ 3.90)。结论HPSE Arg307Lys与中国北方地区急性白血病的发生可能无关。     

Allogeneic bone marrow transplantation in Korea: 1983-92

Between March 1983 and December 1992, we performed 178 allogeneic BMTs for patients with hematopoietic stem cell disorders: 48 acute myelogenous leukemia (AML), 27 acute lymphoblastic leukemia (ALL), 40 chronic myelogenous leukemia (CML), 55 severe aplastic anemia (SAA), 6 myelodysplastic syndrome (MDS), 1 non-Hodgkin's lymphoma and 1 hybrid leukemia. Twenty-five of 48 AML are in disease-free survival (DFS). Fifteen of 27 ALL are in unmaintained remission. Twenty-four of 40 CML are in DFS. Forty-four out of 55 SAA patients are alive and well. Comparing the survival between standard (< or = CR1: 21 of 31 (68%)) and high risk (> or = CR2: 4 of 17 (24%)) AML, our data suggest that the preparative regimen for high risk AML was not potent enough to eradicate the residual disease in advanced AML. Although our cases are limited and the follow-up period is short, the result of ALL (overall: 56%, standard risk (adult < or = CR1, children < or = CR2: 10 of 14 (71%) and high risk (adult > or = CR2, children > CR2): 5 of 13 (38%)) and CML (overall: 60%; CP: 19 of 27 (70%), AP or BC: 5 of 13 (38%)) are promising. The probability of 5 year survival of SAA was 80 +/- 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute myeloblastic leukemia associated with an intermediate state between the healthy carrier state and adult T-cell leukemia

This report describes an intermediate state between the human T-cell lymphotropic virus type I (HTLV-I) healthy carrier and adult T-cell Leukemia (ATL) who developed acute myeloblastic leukemia (AML, FAB subtype M2). The polyclonal integration of HTLV-I proviral DNA was demonstrated in the peripheral blood lymphoid cells, whereas AML cells had no HTLV-I proviral DNA. The patient achieved remission after combination chemotherapy but cells with lobulated nuclei persist at a low level and the polyclonal integration of HTLV-I proviral DNA is still demonstrated. We suggest that the patients with the integration of HTLV-I proviral DNA might develop secondary neoplasms more frequently than healthy carriers and this case stresses the need to exercise caution with these patients. The relationship between HTLV-I and AML is briefly discussed.     

Effects of gestation age and of birth weight in the concentration of carnitine in the umbilical plasma

36 patients with relapsed (29) or refractory (7) acute lymphoblastic or nonlymphoblastic leukaemia received regimens employing 1-3 courses of mitoxantrone (or idarubicin), intermediate doses of cytarabine and etoposide. Complete remission (CR) was achieved in 30% of patients (5/15 ALL, 6/21 AML, 5 cases of refractory and 6 of relapsed leukaemia). Duration of CR was 3-6+ months (3 patients are still alive). Toxicity of the treatment was acceptable, however 5 patients with severe granulocytopenia died from sepsis.     

Adult acute leukemia

Untreated acute leukemia is a uniformly fatal disease with a median survival time shorter than 3 months. Current treatment strategies provide a significant increase in survival time for most patients, some of whom may be cured. The majority of patients with acute leukemia, however, ultimately die of the disease or complications of treatment. The effective treatment of acute leukemia requires (1) differentiation of acute myeloid leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognition of clinically relevant subtypes; (2) identification of patients who are more likely or less likely than average to benefit from a conventional treatment; and (3) selection of therapy that provides a reasonable likelihood of response with acceptable risk of toxic effects. The diagnosis of acute leukemia is established in most cases by a bone marrow aspirate that demonstrates at least 30% blast cells. The traditional criteria to distinguish between AML and ALL rely on morphology and cytochemical reactions. Immunologic analysis of antigen expression and analysis for numerical or structural chromosomal abnormalities of leukemia cells are routinely feasible. Karyotypic analysis is of prognostic importance and should be performed on all diagnostic specimens of bone marrow aspirate. Immunophenotypic analysis may be useful to confirm the disease classification in selected cases. The importance of the routine immunophenotypic characterization of acute leukemia, however, is controversial. The subtypes that must be recognized because of the need for specific treatment include (a) acute promyelocytic leukemia (APL), which is the M3 subtype of AML, and (b) the L3 subtype or mature B-cell ALL. Induction therapy for acute leukemia is treatment intended to achieve induction of complete remission (CR). Complete remission is defined as the absence of morphologic evidence of leukemia after recovery of the peripheral blood cell counts. Failure to achieve CR may be attributed to death during chemotherapy-induced bone marrow hypoplasia or to drug resistance manifested either as failure to achieve hypoplasia or as persistent leukemia after recovery from hypoplasia. Postremission therapy is treatment administered in CR to prevent or delay relapse of the leukemia. However, the majority of patients have disease relapse. Intensification of therapy is a treatment strategy designed to overcome resistance to chemotherapy. Recent clinical trials of intensified induction or postremission therapy suggest improved outcome. However, the toxic effects of dose intensification can be substantial, limiting any potential benefit of this approach. Identification of prognostic factors may allow one to estimate the likelihood of an outcome, to determine an optimal treatment strategy. It is well established that age at the time of diagnosis, leukemia cell karyotype, and whether the leukemia is de novo or secondary are factors that influence treatment decisions. Patients with favorable prognostic factors should probably receive conventional therapy. Patients with unfavorable prognostic factors have shown little benefit from conventional therapy. In addition, factors that indicate poor outcome with conventional therapy are also predictive of poor outcome with intensified therapy. Consequently, these patients should be considered for investigational therapeutic strategies. The bias may be to counsel them to accept the potential increased morbidity of such treatment before there is definite evidence of the possibility of improved outcome. Induction chemotherapy for younger patients with AML (less than 55 years of age) in general consists of one or more courses of cytarabine (ara-C) and an anthracycline or an anthracycline derivative. Randomized trials have failed to confirm that treatment with either etoposide or high-dose ara-C induces disease remission. Patients with secondary AML, high levels of CD34 antigen expression, or an unfavorable karyotype, however, may benefit from ind     

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.     

Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16 patients

Sixteen patients with relapse after allogeneic BMT were treated with donor leukocyte infusions (DLI) from the original donor. The diagnoses at relapse were: CML in chronic phase (CP) (two patients), CML in accelerated phase (AP) (four patients), AML (four patients), MDS (one patient), ALL (four patients) and relapse of Hodgkin's disease (one patient). The patients received a mean of 5.2 x 10(8) leukocytes/kg with a range of 1.4-12.3 x 10(8) leukocytes/kg. Six patients obtained complete remission (CR), one with CML in CP, three with CML in AP, one MDS and one ALL. Partial remission (PR) was seen in three patients, one patient with CML in AP, one with AML and one with Hodgkin's disease. Seven patients had no response (NR) to the infusions, including one patient with CML in CP transplanted with a syngeneic donor. Four patients developed marrow hypoplasia after DLI (three CR and one PR) and two patients (ALL with CR and MDS with CR) were hypoplastic at relapse and marrow hypoplasia continued after DLI. GVHD occurred without GVL, but GVL only occurred in one patient with absence of GVHD. Eleven patients died of leukemia, six patients are alive. Three patients with CML are in CR 12, 12 and 32 months after DLI and one patient with ALL is in CR 15 months after DLI.     

Two conformational states of Candida rugosa lipase

A retrospective analysis was performed on 235 elderly acute myelogenous leukaemia (AML) patients aged 60 years or more, consecutively admitted to a single haematological department during a 10-year period from 1980 to 1989. 46% of patients received only conventional induction chemotherapy. The rate of inclusion in EORTC cooperative clinical trials was significantly lower than for younger patients despite specific protocols proposed for the elderly since 1983, thus confirming the important selection bias of most published series on elderly AML patients. Compared with treatment results in patients < 60 years, complete remission (CR) rate was lower (33.3% v 65.4%, P < 0.0001), with a marked drop in patients older than 70, and induction death rate was higher (21.3% v 12.5%, P = 0.04). Intrinsic characteristics of leukaemic cells, especially expression of the MDR1 gene, in vitro growth of the leukaemic clonogenic cells and sensitivity to daunorubicin-(+)cytosine arabinoside, did not differ according to age, except that there was a higher incidence of previous myelodysplastic syndromes and a lower incidence of good prognostic cytogenetics in the elderly patients. Thus, treatment failure in elderly AML patients appears to be mainly due to host-related factors (especially performance status and age < or > or = 70 years), and to inadequate treatments. Some elderly patients may have been undertreated because of the planned anthracycline dose reduction, resulting in a higher rate of 'resistant' AML, i.e. patients surviving the induction period without entering into CR, than in younger patients (45.4% v 22.1%, P < 0.0001). 11 patients (4.7%) with untreated or 'resistant' AML survived more than 1 year, while receiving only supportive care. These slowly progressive AML patients were characterized by a good performance status, and lower circulating blast cells and bone marrow blast counts.     

HAG预激化疗作为诱导缓解方案治疗老年人急性髓系白血病和骨髓增生异常综合征的临床观察

目的 观察HAG预激化疗作为诱导缓解方案在治疗老年急性髓系白血病(AML)和骨髓增生异常综合征-难治性贫血伴原始细胞增多型(MDS-RAEB)患者中的疗效.方法 对应用HAG预激方案治疗的21例AML和9例MDS-RAEB患者(≥60岁)的临床资料进行回顾性总结,包括疾病完全缓解(CR)率、有效率以及不良反应.结果 21例老年AML患者中,HAG诱导缓解的有效率为66.7%(14/21),其中CR率为47.6%(10/21);9例老年MDS-RAEB患者中,CR率为55.6%(5/9):HAG预激化疗的主要不良反应为因骨髓抑制继发的感染,调整化疗方案后所有患者均能耐受.结论 HAG预激化疗作为诱导缓解方案适用于老年AML和MDS-RAEB患者.     

伴NPM1基因突变的成年人急性髓系白血病临床研究

目的 探讨我国成年伴NPM1基因突变的急性髓系白血病患者(NPMc+AML)的临床特点,初步探讨定期定性检测该突变在早期判断AML复发中的意义.方法 采用聚合酶链反应(PCR)-毛细管电泳法对95例成年初治AML患者检测NPM1突变情况,并选取其中5例完全缓解患者定期检测该突变.结果 95例成年AML患者NPM1突变发生率为29.5%(28/95);≥40岁患者突变发生率[40.0%(22/55)]明显高于＜40岁患者[15.0%(6/40)](λ 2=6.963,P=0.012);正常核型AML患者突变发生率[51.1%(24/47)]明显高于异常核型患者[8.3%(4/48)](λ2=20.860,P=0.000).AML患者发生NPM1突变以M5[72.7%(16/22)]、M2[36.3%(8/22)]常见,在具有重现性染色体异常的AML中,未发现该突变.NPMc+AML患者白细胞、血小板计数及乳酸脱氢酶水平均明显高于NPMc-AML组(t值分别为4.132、4.603、4.069,均P＜0.05).NPMc+AML患者完全缓解率、无复发生存率及总生存率均明显高于NPMc-AML患者(λ2值分别为10.448、4.146、4.384,均P＜0.05).定期检测的患者血液学复发前1.5～2.0个月草新出现NPM1基因突变.结论 NPM1基因突变在成年AML患者中,尤其是正常核型AML患者中有较高的发生率,临床表现为患者年龄偏大,白细胞计数、血小板计数、乳酸脱氢酶均较高,NPM1基因突变是成年AML患者预后良好的指标.定期定性监测该突变可早期判断AML复发.     

Paratesticular rhabdomyosarcoma in adult patients: 16-year experience at Institut Gustave-Roussy

BACKGROUND: Children with paratesticular rhabdomyosarcoma (RMS) have both a good prognosis and a high survival rate. The clinical behaviour and outcome of the disease in adults is not well described. PATIENTS AND METHODS: We reviewed retrospectively our experience with paratesticular RMS in patients older than 16 years during a 16-year period (1975-1991). RESULTS: Thirteen adult patients with paratesticular RMS are reported. Median age was 21 years (range 16 to 31). Presentation characteristics were scrotal mass in 11 cases, lumbar pain and weight loss in 5 cases, hypercalcemia in 3 cases and thrombocytopenia in 3 cases. There were 5 patients with stage IV, 2 with stage IIB and 6 with stage IA (IRS classification). The 5 stage IV patients are reported in detail, with initial bone marrow infiltration encountered in 4 of them. Objective response to chemotherapy was achieved in all 6 patients with measurable disease (2 CR + 4 PR). Two of 7 patients who received adjuvant chemotherapy relapsed at 7 and 11 months. After a median follow-up of 90 months, 8 patients (5 stage IV, 3 stage IA) died from disease progression. CONCLUSION: Metastatic disease with bone marrow involvement at presentation and aggressive behaviour seem to be more relevant in adult paratesticular RMS patients compared with children.     

Serum levels of p55 and p75 soluble TNF receptors in adult acute leukaemia at diagnosis: correlation with clinical and biological features and outcome

The tumour necrosis factor (TNF)/TNF-receptor (TNFR) complex plays a role in the growth of leukaemic cells. We retrospectively investigated the relationship between pretreatment serum concentration of soluble TNFR (p55- and p75-sTNFRs) and outcome in adult acute myeloid (AML 82 cases) and lymphoid (ALL 44 cases) leukaemia. Both sTNFRs were significantly higher in AML (p55-sTNFR 4.53 +/- 3.7, median 3.75; p75-sTNFR 6.51 +/- 5.25 ng/ml, median 4.72) and ALL sera (3.31 +/- 1.5, median 2.95; 5.30 +/- 2.3 ng/ml, median 4.56, respectively) than in controls (1.89 +/- 0.5, median 1.98; 2.22 +/- 0.8 ng/ml, median 2.37) (P < 0.01 for both sTNFRs). Fresh leukaemic cells expressed p55- and p75-sTNFRs, which were modulated and released into the supernatant (SN) following short-term in vitro culture, suggesting that in vivo sTNFRs were also leukaemia-derived. Whereas no correlation was observed between sTNFRs and outcome in ALL, in AML higher p55-sTNFR levels (> 3.75 ng/ml) were associated with shorter disease-free survival (DFS) (P = 0.006) and overall survival (OS) (P = 0.0004). At multivariate analysis p55-sTNFR was the most significant predictor of DFS (P = 0.006) and OS (P < 0.001). Our data suggest that the prognostic significance of p55-sTNFR in AML could be related to relevant biological features of AML blasts.     

Insufficient understanding of second tumors after childhood neoplasms in Switzerland

Second malignancy after childhood neoplasms is a well-known complication. However, frequency differs considerably according to the types of primary neoplasm and the specifics of therapy. Ten patients with a second malignancy after being cured of the primary tumor are described. There were 2 patients with acute lymphoblastic leukemia, one with non-Hodgkin's lymphoma, and one with breast cancer after Hodgkin's disease. Two patients with heritable retinoblastoma developed osteosarcomas in the irradiation field after a latent period of 7 and 14 years respectively. There was another osteosarcoma in a Wilms' tumor survivor. One patient with acute lymphoblastic leukemia developed a secondary AML 10 years after achieving initial remission, and a meningioma was diagnosed in another patient with cured acute lymphoblastic leukemia. One patient died of peritoneal sarcomatosis of unknown origin 20 years after the diagnosis of acute myeloid leukemia. All patients received radiotherapy for the primary neoplasms. Secondary neoplasms in other patients were probably missed because they occurred in adulthood when the patients were transferred to other medical centres. It is impossible to trace these patients because central registration of patients with neoplasms is lacking. It is therefore important to establish a central cancer registry for the whole of Switzerland. Second malignancy after childhood cancer is not a rare event and requires long-term follow-up of patients with neoplasms.     

Philadelphia chromosome-positive (Ph+) childhood acute lymphoblastic leukemia: good initial steroid response allows early prediction of a favorable treatment outcome

Among 4,760 acute lymphoblastic leukemia (ALL) patients enrolled from 1986 to 1995 in two subsequent trials of the BFM and AIEOP study group, 61 patients were found to have Philadelphia chromosome-positive (Ph+) ALL. These patients were analyzed for presenting features and treatment outcome to identify specific prognostic factors. Treatment stratification was based on initial cell mass and early response as determined by blast count in peripheral blood after a 7-day induction prephase with prednisone and one dose of intrathecal methotrexate on day 1. All patients were treated by similar intensive Berlin-Frankfurt-Münster (BFM) protocols. The median age of Ph+ patients was 7.5 years, the median white blood cell count (WBC) was 75 x 10(9)/L, 77% of patients had common ALL, and 29% coexpressed myeloid markers. After a median observation time of 4.2 years, 29 of 61 patients are alive (survival probability [pSUR] at 4 years, 0.49; standard error [SE], 0.06), and 24 of 61 are in first complete remission (CR1; probability of event-free survival [pEFS] at 4 years, 0.38; SE, 0.06). Twenty (35%) of 57 evaluable patients had >/=1,000 leukemic blasts per microliter of blood on day 8 of induction (defined as prednisone-poor-response [PPR]). These patients were older (10.0 v 6.88 years; P = .02) and had a higher WBC (144 v 29 x 10(9)/L; P = .0016) as compared with patients with prednisone good response (PGR; <1,000 blasts/microL at day 8). Only 2 of 20 patients (10%) with PPR remained in CR1 and alive: 6 patients with PPR did not survive after allogeneic bone marrow transplantation (BMT) due to recurring disease (n = 3) and toxicity (n = 3), and 12 nontransplanted patients died due to progression (n = 5) or relapse (n = 7). In contrast, 26 (70%) of the 37 patients with PGR are alive. Of 18 patients transplanted by allo-BMT, 1 relapsed (now in CR2) and 4 died after BMT. Among the 19 patients with PGR treated by chemotherapy alone, 8 remained in CR1 and 11 relapsed, of which 4 are in CR2 or CR3. The prednisone response emerged as the only independent prognostic factor for survival in Cox regression analysis. Thus, two thirds of Ph+ childhood ALL cases can be identified early by PGR, which, when treated with intensive BFM chemotherapy, with or without BMT, have a significantly lower risk of treatment failure. With a median continuous complete remission (CCR) time of 4.1 years, pEFS for PGR is 0.55 (SE, 0.08) compared with 0.10 (SE, 0.07) in patients with PPR (P = .0001). PGR is also an indicator for treatment responsiveness and durable second remission after relapse, which in turn may provide a second chance for BMT.     

Phase II-trial of double-consolidation following intensive induction treatment for improvement of survival in elderly patients with acute myeloid leukemia

Thirty-two consecutive, unselected acute myeloid leukemia (AML) patients (pts) of all FAB-subtypes with a median age of 68 years were treated with intensive induction chemotherapy consisting of one or two cycles of daunorubicin 30 mg/m2 day 1-3 and Ara C 100 mg/m2 as continuous infusion day 1-7. The overall CR rate was 50%, 14/24 (58%) in de novo AML, and 2/8 (25%) with preceding MDS. One patient achieved a PR of 21 months duration, 3 pts died within 7 days of the induction treatment (ED), 6 died during hypoplasia (HD), and 6 remained refractory to 2 cycles of induction. Four pts died after achieving CR. Of the remaining 12 responders, 11 pts received 2 cycles of consolidation consisting of daunorubicin 30 mg/m2 day 1, and Ara C 100 mg/m2 continuous IV infusion day 1-7. No deaths were observed during consolidation. DFS and survival of responders were 7 and 13 months respectively, survival of all pts, responders and non-responders, was 7 months. Large cooperative trials are necessary to identify those elderly pts who may benefit from intensified consolidation treatment.     

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures

The percentage of long-term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known. Between 1981 and 1996 we treated 99 patients with de novo MDS who had high-risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy. After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant). Of the 71 patients treated before 1993, with sufficient follow-up, 10 (14%) had survived > 4 years (long-term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49-78 months. Long-term survivors were characterized by a significantly higher incidence of RAEB-T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB-T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years. Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long-term survivors remains low, however, and is almost restricted to patients with RAEB-T at diagnosis and no unfavourable karyotype.     

Classification of ninety-eight adult cases of acute leukemia according to morphology, immunology and cytogenetics]

Ninety-eight cases of adult acute leukemia (AL) were diagnosed and classified based on morphologic, immunologic and cytogenetic (MIC) features. The results showed that: the conformity rate of cytomorphologic/cytochemical classification with MIC classification was 90.8%. For ALL, the conformity rate of immunologic classification with MIC classification was 95.6%, but it was only 70.8% for AML. Of the 48 AML, 10 expressed lymphoid lineage, associated antigens and 8 of 43 ALL expressed myeloid lineage-associated antigens. Seven cases were diagnosed as hybrid acute leukemia according to Catovsky criterion. The chromosome aberrations were found in 70 cases, of them 46 cases showed characteristic abnormalities including t(9;22), t(4;11), t(11;14), t(8;12), t(8;14), 6q-, 9p-, and t(15;17), t(8;21), inv(16), etc.     

Autologous bone marrow transplantation with monoclonal antibody purged marrow for children with acute lymphoblastic leukemia in second remission. Spanish Working Party for BMT in Children

The purpose of this study was to evaluate the outcome of children with acute lymphoid leukemia (ALL) in second remission who have undergone high-dose chemotherapy and radiotherapy and autologous bone marrow transplantation (ABMT) with monoclonal antibody purged marrow, and to determine the main prognostic factors. From 1987 to 1992, 55 children with ALL in second remission underwent ABMT. The conditioning regimen consisted of total body irradiation (TBI) plus cyclophosphamide in 21 patients and TBI plus cyclophosphamide plus cytarabine or VP-16 in 28 patients; the remaining six patients were treated with chemotherapy alone (cyclophosphamide and busulfan, and/or VP-16). The marrow was purged using monoclonal antibodies and complement or magnetic microspheres in all cases. All patients engrafted. Three patients (5%) died early post transplant from infections. Twenty-six patients (47%) relapsed (median 150 days); 26 patients (47%) are alive and in complete remission (CR) at a median of 36 months. The Kaplan-Meier estimation showed a probability of event-free survival (EFS) of 46 +/- 0.007%. In the univariate analysis, first CR length and conditioning with TBI plus two or more cytotoxic drugs were found to be the most significant predictors of EFS. ABMT with purged marrow is a treatment modality which offers a chance of cure in children with ALL after relapse, including children who relapse early.     

Nucleolar organizer region counts predict complete remission, remission duration, and survival in adult acute myelogenous leukemia patients

PURPOSE: The analysis of the nucleolar organizer regions (AgNORs) was performed in patients with acute myelogenous leukemia (AML) to verify the role of cell proliferation in predicting complete remission (CR) and survival. MATERIALS AND METHODS: Bone marrow biopsies from 40 adult patients with AML were stained with the argyrophilic method. The mean AgNOR number (AgNOR count) was calculated for each case. After induction therapy, patients who achieved CR received intensive consolidation; two underwent autologous and four allogeneic bone marrow transplantations (BMT). RESULTS: The mean AgNOR count for the whole series was 6.6 (SD = 1.35); it was higher in CR patients than in resistant ones (P = .02). The median duration of CR was 26 months for patients with an AgNOR count greater than 6.6, but only 6 months for those with lower counts (P = .01). Sixteen patients who achieved a CR relapsed and 14 reached a second CR; the median duration of second CR was 16 months for patients with AgNOR count greater than 6.6, but only 5 months for those with lower counts (P = .01). The median survival time for the whole series was 14 months, with 30% of patients alive and in continuous CR at 103 months. Survival was longer for patients with an AgNOR count greater than 6.6 (33 months) than for those with lower counts (6 months; P = .0009). In multivariate analysis, when CR was excluded from the model, AgNOR count appeared as an independent prognostic variable (P = .005). CONCLUSION: AgNOR analysis is a suitable method to assess cell proliferation in bone marrow biopsies and can predict CR, remission duration, and survival in AML patients.