Evaluation of 58 patients with acute leukemia]

We made a retrospective study of 44 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) admitted to our hospital from September 1984 to May 1991. The complete remission (CR) rate of ANLL was 90.9%, against 85.7% for ALL. The 5-year survival of ANLL was 50.7%, and that of ANLL under age 60 years was 70.3%. The 2-year median survival of ALL was 35.1%. These results were obtained with response-oriented individualized therapy, and intensive chemotherapy with a view to eradication of residual leukemic cells. Eight elderly patients with ANLL were treated with cytosine arabinoside in low doses. Complete remission was achieved in 6 patients, but these cases relapsed. These treatments should be reconsidered for long CR duration. Our schedules of response-oriented individualized therapy were too flexible to apply at another institute so they should be arranged for general application.     

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.     

Cytogenetics and their prognostic value in childhood and adult acute lymphoblastic leukemia (ALL) excluding L3

Cytogenetic analysis was made at diagnosis in 174 cases of ALL (101 children less than 20 years and 73 adults), excluding Burkitt's ALL (L3). In 11 children (11 per cent) insufficient material was obtained. In the remaining 90, 50 (56 per cent) had a normal karyotype, 20 (22 per cent) a hyperdiploid karyotype, five (6 per cent) a hypodiploid karyotype, 12 (13 per cent) had a translocation (including seven cases of t(1;19)) and three had a pseudodiploid karyotype without translocation. Ninety-eight per cent of patients reached complete remission (CR). Median actuarial CR duration was not attained, was 50 months, 13 months and 11 months respectively in patients with hyperdiploid, normal, hypodiploid karyotype and in patients with a translocation, the difference between subgroups being significant. In a Cox model, cytogenetics were the strongest factor predicting CR duration (p = 0.03) followed by leukocytes (p = 0.04), whereas the presence of ‘bulky disease’ had a borderline value (p = 0.077). Of note was that 9/17 (53 per cent) patients with a hypodiploid karyotype or a translocation had no ‘risk factors’ before cytogenetic analysis. In adults, cytogenetic analysis was unsuccessful in 15 (20 per cent) of patients. In the remaining 58 cases, 19 (33 per cent) had a normal karyotype, 15 (26 per cent) had a hyperdiploid, one (2 per cent) had a hypodiploid karyotype, 19 (33 per cent) had a translocation (including 12 t(9;22)), and four (7 per cent) had a pseudodiploid without translocation. 73 per cent patients reached CR. Median actuarial DFS was 12.5 months. No significant differences in CR rate and CR duration were seen between cytogenetic groups, but median CR duration was slightly longer in patients with a normal karyotype (17 months) and shorter in patients with t(9; 22) (8.5 months). Only 3/12 of the latter had major risk factors before cytogenetic analysis. Cytogenetic analysis is important in ALL, especially in patients with otherwise standard risk factors, as it may reveal unexpected translocations or hypodiploidy, which may require a therapeutic reinforcement.     

Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia: a single-centre experience.

Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA-identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy-TBI (n = 15), VP16-Cy-TBI(n = 12), CBV (n = 1) and Bu-Cy (n = 1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease-free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4-years DFS of 42.3 per cent. Three patients died of transplant-related complications before 100 days. Relapse occurred in 11 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment-related complications. There were 13 survivors (median follow-up 38 months, range 12-98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p = 0.39). No long-term DFS is obtained from patients with resistant disease (n = 4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p = 0.29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA-matched siblings, the option of BMT should be considered in light of local consolidation survival results.     

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.     

Allogeneic bone marrow transplantation versus chemotherapy for the treatment of childhood acute lymphoblastic leukemia in second remission: a single-institution study.

PURPOSE: A retrospective analysis of the treatment of childhood acute lymphoblastic leukemia (ALL) in second remission (CR2) was undertaken at our institution to compare the outcome and prognostic factors of patients treated with chemotherapy or allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventy-five children who suffered a medullary relapse and achieved a second remission were treated with either an unmodified allogeneic HLA-matched sibling BMT after hyperfractionated total body irradiation (TBI) and cyclophosphamide (n = 38) or chemotherapy according to institutional chemotherapy protocols (n = 37). To avoid the bias of survival from the attainment of second remission in favor of BMT, the final comparative statistical analysis used the landmark approach and comprised 37 and 29 patients from the BMT and chemotherapy groups, respectively RESULTS: The disease-free survival (DFS) rate was 62% and 26% at 5 years, respectively, for the BMT and the chemotherapy groups (P = .03), with relapse rates of 19% and 67%, respectively, for these two groups (P = .01). There was an overall advantage for the BMT therapeutic approach, as compared with chemotherapy, for patients with ALL in CR2 (1) for patients with a WBC count (at diagnosis) of 20 x 10(9)/L or higher (DFS, 40% v 0%) and those with a WBC count of less than 20 x 10(9)/L (DFS, 73% v35%), (2) for patients whose duration of CR1 was less than 24 months (DFS 48% v 9%) and for patients whose duration of CR1 was 24 months or longer (DFS, 81% v 37%) and (3) for patients who were initially treated with intensive regimens incorporating more than five chemotherapy agents (DFS, 57% v 20%) and for patients treated with five agents or fewer (DFS, 72% v 32%). CONCLUSION: In our single-institution series, unmodified HLA-matched allogeneic sibling transplants using hyperfractionated TBI and cyclophosphamide for patients with ALL in CR2 have resulted in superior outcome with a significantly improved probability of DFS and a lower relapse rate, as compared with those for patients treated with chemotherapy, regardless of the duration of first remission, the disease characteristics at diagnosis, or the intensity of prior treatment during first remission.     

Intensive chemotherapy for acute non-lymphoblastic leukemia after primary myelodysplastic syndrome

Twenty-five patients with a primary myelodysplastic syndrome (MDS) transformed into acute non-lymphoblastic leukaemia (ANL) were treated with intensive chemotherapy. A complete remission (CR) was obtained in six patients (24 per cent). In five of these six patients two courses of chemotherapy were needed to achieve CR. In eight patients chemotherapy cleared the bone marrow of blasts, but the aplasia was fatal. A partial effect on bone marrow blasts was seen in four patients and no effect in another six. Eleven patients (44 per cent) died from the consequences of chemotherapy-induced cytopenia. A short interval between MDS and transformation into ANL was associated with a better chance of achieving complete remission. Age, karyotype, type of MDS, peripheral blood or bone marrow findings had no influence on the result of chemotherapy. The median survival from start of treatment was 5 months (range 0.5-24 months). In the patients who achieved a CR, the median duration of the remission was 7 months (range 3-12 months). The poor response rate, the short duration of the remissions and the high treatment-related mortality suggest that current intensive anti-leukemic chemotherapy in ANL after primary MDS is of limited benefit.     

成人急性白血病强化治疗67例预后分析

目的：观察成人急性白血病（ＡＬ） 患者完全缓解（ＣＲ） 后强化治疗的效果。方法：对６７ 例ＣＲ后的成人ＡＬ患者进行强化治疗,急性髓细胞性白血病（ＡＭＬ）以中剂量阿糖胞苷（ＩＤ－ Ａｒａ－ Ｃ）方案为主,急性淋巴细胞性白血病（ＡＬＬ）以中剂量氨甲蝶呤（ＩＤ－ ＭＴＸ）方案为主。结果：４８ 例ＡＭＬ患者中位ＣＲ 期１６ 个月,预期３ 年和４ 年无病生存（ＤＦＳ）为３６９％ 和２１１ ％ ;２３ 例（４７９ ％） 患者复发。１９ 例ＡＬＬ 患者中位ＣＲ 期１４ 个月,预期４ 年ＤＦＳ 为３１５％ ;１０ 例（５２６％ ） 患者复发。结论：以ＩＤ－ Ａｒａ－ Ｃ 为主的强化方案及以ＩＤ－ ＭＴＸ 为主的强化方案分别能延长ＡＭＬ及ＡＬＬ患者的ＤＦＳ,降低复发率     

ALL-TRANS RETINOIC ACID (ATRA) IN THE TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APL)

Acute promyelocytic leukemia is characterized by the reciprocal translocation of chromosomes 15 and 17. All-trans retinoic acid (ATRA) efficiently induces differentiation of the abnormal promyelocytes. In this study, we had used ATRA as the primary induction therapy for 17 newly diagnosed patients, and as the salvage therapy for 11 patients who relapsed from or were resistant to chemotherapy. All patients received subsequent consolidation chemotherapy. Complete remission (CR) rate, early death rate (within 28 days of diagnosis) were then compared to an historical control of 50 APL patients treated with combination chemotherapy; and event-free survival of the 17 newly diagnosed patients was compared to the historical control. In the ATRA group, 26 of the 28 patients (93 per cent) attained complete remission. Two of 28 (7 per cent) died within 28 days of ATRA therapy. There was no case of primary resistance to ATRA. Combination chemotherapy was added to ATRA in five patients due to rapidly increasing leucocyte count. There was one case of retinoic acid syndrome which resolved with steroid. When compared to the 50 cases of historical control, there is significant improvement in the overall CR rate (92 per cent versus 59 per cent, p=0·001) and a significant reduction in the early mortality rate (7 per cent versus 41 per cent, p=0·001). Moreover, when the survival result of the 17 newly diagnosed patients were compared with the control, there is a significant improvement in the projected EFS at 3 years (64 per cent versus 25 per cent, p=0·007). In conclusion, ATRA was showm to improve the CR rate, reduce induction mortality and significantly prolong the event-free survival.     

Non-Hodgkin's lymphoma of unfavourable histology: a multivariate analysis of factors predicting the response to CHOP

Forty-eight patients with de novo non-Hodgkin's lymphoma (NHL) of unfavourable biology received CHOP as first-line chemotherapy. A complete remission (CR) was achieved in 64.5 per cent patients. Overall 4-year projected survival was 48 per cent with a median follow-up of 40.5 months. Two pretreatment characteristics, high LDH serum levels and bulky abdominal disease, were negatively associated with survival at the proportional hazards regression model and were used to calculate each patient's relative-risk. Such analysis allowed to identify two prognostic subgroups according to their outcome to CHOP. Firstly, a high-risk subgroup that showed an 8 per cent CR rate, most patients dying within the first year after diagnosis. Secondly, a low-risk subgroup that showed an 83.5 per cent CR rate and a 4-year project survival of 66 per cent. From the above results two major conclusions can be drawn: (1) the CHOP combination is an effective treatment for unfavourable NHL patients with a low relative-risk and (2) new therapeutic approaches should be explored for NHL patients with a high relative-risk at diagnosis.     

Improved treatment outcome in adult acute lymphoblastic leukemia using the intensive German protocol,a preliminary report

Thirty-nine consecutive patients with acute lymphoblastic leukemia were treated with an intensive chemotherapy protocol. There were 23 males and 16 females with a median age of 37 years (range: 15–65). Eighteen patients had common ALL, seven had pre-B ALL, three earlyprecursor B ALL, seven T-ALL and four had aberrant expression of myeloid antigens (c-ALL in three and pre-B ALL in one). The median initial leukocyte count was 11.8×10⁹/l (range: 0.65–295). Cytogenetic result of the marrow was available in 16 of 39 patients (41 per cent) and showed Philadelphia positivity in six, a normal result in six and one each of t(4,11), t(1,19), hyperdiploidy and del 12p. Hepatosplenomegaly was present in about 20 per cent of the patients. l-Asparaginase-related hepatic toxicity was the commonest toxicity (48.7 per cent) during phase I of induction. Prolonged pancytopenia and hypoplastic death were common during phase II. With the use of growth factors during the neutropenic period of phase II induction, the rate of hypoplastic death was reduced from 40 per cent to 3 per cent. Common causes of treatment failure included early hypoplastic death (27.8 per cent) and leukemia relapses (50 per cent) while primary refractory leukemia, hepatic failure and perforated peptic ulcer contributed to 11.1, 5.5 and 5.5 per cent of the other deaths. A high complete remission (CR) rate (87·4 per cent) was achieved after phase I induction. The median event-free survival (EFS) was 8 months and the 3-year event-free survival was 43 per cent. This result compared favourably to the other regimens previously employed in our institution. In conclusion, satisfactory survival can be achieved with this intensive regimen. Good supportive care was however, essential to minimize toxicities. © 1997 John Wiley & Sons, Ltd.     

A phase II trial of ProMACE-CytaBOM in previously untreated non-Hodgkin's lymphoma of intermediate- or high-grade histology.

Between November 1985 and June 1989 the aggressive combination chemotherapy programme ProMACE-CytaBOM was used at a community-based hospital as primary treatment for non-Hodgkin's lymphoma (NHL) of intermediate or high-grade histology in Ann-Arbor stages IB-IV. The 53 patients entering the study represented 90 per cent of all consecutive eligible patients with NHL diagnosed during the time period considered. Their median age was 54 years and median observation time was 36 months. Of 50 patients evaluable for response, 35 (70 per cent) achieved complete remission (CR), seven (14 per cent) partial remission, and five (10 per cent) were refractory. Treatment was given on an outpatient basis. Actually delivered drug doses ranged from 88 per cent to 97 per cent of the theoretical doses. Life-threatening toxicity was experienced by four patients. Treatment was stopped in three cases (6 per cent) because of toxicity and there was one treatment-related death. Actuarial 2-year disease-free survival of patients in CR was 73 per cent. Overall actuarial 3-year survival and disease-free survival were 67 per cent and 51 per cent respectively. High LDH level was a significant adverse prognostic factor both for achievement of CR (P less than 0.005) and for survival (P less than 0.0002). Age was of no prognostic importance. We conclude that ProMACE-CytaBOM is an effective, easy to administer and well-tolerated regimen for patients with aggressive NHL.     

Intensive chemotherapy for peripheral T-cell lymphomas.

Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan-Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty-five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than those with stage IV disease but the relapse rate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.     

Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period.

Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follow-up data. The analysis included data on 351 patients treated by standard chemotherapy according to 11 different successive and/or concomitant regimens. Complete remission (CR) was achieved in 299 patients (79%). Initial performance status, LDH level, immunophenotype, age, and risk group (defined according to Hoelzer's criteria) at diagnosis were of significant prognostic value for CR achievement. Median leukemia-free survival (LFS) was 14 months with a 3-year, a 5-year, and an 8-year LFS at 30%, 26%, and 24%, respectively. LFS was better in T cell lineage ALL than in B cell lineage ALL (P = 0.05). Younger age was also a favorable prognostic factor for LFS (P = 0.001). Philadelphia-positive (Ph+) ALL displayed a poor outcome since median LFS was 7 months with only 13% of survival at 3 years. Median overall survival (OS) of the entire cohort was 18 months with a 3-year, a 5-year, and an 8-year OS at 32%, 24%, and 22% respectively. Favorable prognostic factors for OS were younger age (P < 0.0001), and T cell lineage ALL (P = 0.001). Among non-T cell lineage ALL, standard-risk ALL confirmed a significant better outcome than high-risk ALL (P = 0.0003). It was apparent from this analysis that hazard rates for death and relapse were greatest in the first year, decreased substantially between years 1 and 2, then decrease further between years 2 and 3. Rates of death and relapse were quite low after 3-4 years. All patients relapsing after 3 years of CR were B or non-B non-T cell lineage ALL. Long-term survivors (LTS), defined as survival in CR > or =3 years, represented 23% of evaluable patients. Eighty-three patients remain alive in initial CR at >3 years, while only three were LTS after a second CR. Overall, no significant improvement was shown in terms of CR achievement and survival duration over the years. However, regarding survival, a significant improvement was demonstrated in T cell lineage ALL (P = 0.03). Furthermore, patients (aged less than 50 years) transplanted while in first CR did significantly better than those receiving only chemotherapy as post-remission therapy (P < 0.0001). The 3-year OS, after allogeneic transplantation in first CR, was 74% in T cell lineage ALL, while it was less than 50% in B cell lineage ALL. This single center study on a large cohort of ALL patients reflects the degree to which ALL treatment remains unsuccessful in adults. Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR.     

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.     

Acute myeloid leukemia in elderly adults.

One hundred and fifteen previously untreated adults aged over 60 years were referred to St Bartholomew's Hospital between 1978 and 1986 for management of acute myeloid leukemia (AML). Twenty-seven patients received symptomatic or palliative treatment only because combination chemotherapy was considered inappropriate. Eighty-eight patients received intensive chemotherapy with curative intent. There was a 48 per cent 'early death' rate and a 24 per cent incidence of resistant disease; complete remission (CR) was achieved in 25/88 patients (28 per cent). By multivariate analysis, a blast count less than 50 x 10(9)/l at presentation was the only factor predictive for achievement of CR whilst the latter and a presentation blast count less than 50 x 10(9)/l predicted for superior survival. Treatment was often curtailed on account of unacceptable toxicity; only 2/88 patients received the planned six cycles of treatment. Two patients died in CR. Four patients are alive in first CR at 3-9 years from treatment; one is alive in second CR following meningeal relapse. Overall survival was significantly worse than that of a contemporaneous group of adults aged 15-59 years treated at this hospital, but duration of CR was comparable. There are great difficulties involved in the intensive treatment of AML in elderly adults, but the major survival benefit gained by achieving CR should stimulate the search for better tolerated but still curative regimens.     

Phase II study of chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia or lymphoblastic lymphoma: Japan Clinical Oncology Group Study 9004

Granulocyte colony-stimulating factor (G-CSF)-supported, post-remission chemotherapy (Cx) for adult acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) was evaluated. One hundred and forty-three eligible patients (median age, 41 years) including 126 ALL and 17 LBL receiving induction Cx (vincristine, cyclophosphamide, prednisolone [PSL], doxorubicin, L-asparaginase, intrathecal-methotrexate [IT-MTX]) were analyzed. For patients achieving complete response (CR), two courses of post-remission Cx (course A of daunorubicin, cytosine arabinoside, vindesine, PSL plus IT-MTX; course B of mitoxantrone, etoposide, vincristine, PSL plus IT-MTX) with the use of G-CSF were repeated alternately; thereafter, maintenance Cx including MTX and 6-mercaptopurine was given for 2 years. One hundred and nineteen (83%) patients achieved CR, while 14 (10%) died during induction. Among the 119 patients achieving CR, five died in remission, 76 relapsed, and the remaining 38 were alive without disease. The median survival time of the 143 eligible patients was 26 months (95% confidence interval, 19-34). At a median follow-up time of 9 years, the 5-year survival rate was 32% and the 5-year progression-free survival (PFS) rate was 26%. The 5-year survival rate of 36 patients who underwent autologous (n = 20) or allogeneic stem cell transplantation (SCT; n = 16) in the first CR group was 58%. Compared with the authors' previous trials, survival and PFS were markedly improved. In conclusion, G-CSF-supported, intensive post-remission Cx and subsequent SCT are worthy of further investigation for the treatment of adult ALL and LBL.     

Intensive short term therapy with granulocyte-macrophage-colony stimulating factor support, similar to therapy for acute myeloblastic leukemia, does not improve overall results for adults with acute lymphoblastic leukemia. GOELAMS Group.

BACKGROUND: Despite modern treatment programs, less than 20% of adult cases of acute lymphoblastic leukemia (ALL) are cured. For relapsing and/or refractory patients, use of high dose cytosine arabinoside (ara-C) and anthracyclin achieved a complete remission (CR) rate of up to a 75%. The aim of this study was to evaluate in adult patients with ALL 1) the CR rate of a chemotherapy schedule similar to a schedule for acute myeloblastic leukemia (AML) patients, 2) the antileukemic value and the tolerance of 3 intensive stage treatments, and 3) the impact of recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF) on chemotherapy-induced neutropenia and infectious complications, as well as the effect of dose intensity. METHODS: Between November 1990 and April 1992, 67 patients ages 15-55 years with de novo ALL were randomly assigned to receive either rGM-CSF or placebo. The induction treatment consisted of idarubicin, methylprednisolone, and high dose ara-C. After achieving CR, patients up to age 45 years who had an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation (BMT). All remaining patients received a first course of early intensification with high dose ara-C, mitoxantrone, etoposide, and methylprednisolone, followed by autologous, unpurged BMT. RESULTS: Of the 64 eligible patients, 50 (78%) achieved CR. Sixteen allogeneic and 18 autologous BMTs were performed. The median survival was 10.2 months. The 4-year survival was 24%. rGM-CSF only improved the incidence of severe mucositis during the induction course (P = 0.003) and probably also improved the median duration of fever (P = 0.07). CONCLUSIONS: This schedule, similar to that for the treatment of AML patients, with early BMT included, did not prove to be a satisfactory approach to the treatment of most adult ALL patients, although CR was achieved in 78% of cases. In this study, no major improvement was obtained with rGM-CSF therapy.     

Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy.

Thirty-four patients with refractory or recurrent high grade non-Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be 'consolidated' with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment-related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended 'curative' therapy, of whom only four are alive and well 1 year later.     

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.