Patterns of relapse in patients with small cell lung cancer--the effect of chest irradiation and prophylactic cranial irradiation combined with intensive chemotherapy on long-term survival

The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain. Among 27 patients with extensive disease (ED), the chest was also the most frequent site of relapse (44%) followed by the brain (19%). In LD patients who had received chemotherapy plus chest irradiation, the initial relapse rate and the cumulative relapse rate in the chest at 2 years were only 29% and 35.4%, respectively. These rates were significantly lower compared with the rates of 69% and 76.5% for patients who had received chemotherapy alone (p less than 0.05). Survival was improved to some extent by the addition of chest irradiation, but not significantly, however, the long-term survival rate favored those receiving chest irradiation. Prophylactic cranial irradiation (PCI) reduced the frequency of brain relapse and significantly improved the survival of SCLC patients achieving CR. The median survival time and 5-year survival rate of patients who received PCI were 23.1 months and 26.7%, which these figures were only 14.0 months and 8.3% for those who had not respectively. Analysis using Cox's proportional hazard model showed that PCI was the greatest prognostic factor favoring the SCLC patients achieving CR. These results indicate that chest irradiation and PCI in conjunction with intensive combination chemotherapy are effective for cases of SCLC with CR.     

Prognosis of small cell lung cancer with ipsilateral pleural effusion]

A total of 184 patients with small cell lung cancer (SCLC) including 18 patients with ipsilateral pleural effusion as the only evidence of metastasis beyond the primary tumor site (PL), 84 patients with limited disease (LD), and 82 patients with extensive disease (ED) were treated at the Osaka Prefectural Habikino Hospital between December 1982 and June 1990. The median survival time for patients with PL was 51 weeks; for the patients with LD, 51 weeks; and for the patients with ED, 34 weeks. The survival of PL patients was significantly better than that of ED patients (P less than 0.05), and did not differ from that of LD patients. The response rate of PL patients was not significantly different from the response rates observed in LD- and ED-patients. There was no significant difference in survival or response rate between patients with cytologically positive and those with cytologically negative PL. Ipsilateral pleural effusion was not found to be a independent prognostic factor for survival from multivariate analysis in LD patients. These results indicate that the classification of limited disease small cell lung cancer should include patients with ipsilateral pleural effusion, as suggested by the consensus report at the International Association for the Study of Lung Cancer (IASLC) Workshop in 1989.     

Bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Increased risk for relapse associated with T-cell depletion

Data on 405 patients with chronic myelogenous leukemia who received bone marrow transplants in chronic phase were analyzed for factors predictive of outcome. The 4-year actuarial probability of relapse was 19% (95% confidence interval [CI], 12% to 28%) and of survival, 55%. In multivariate analyses the probability of relapse was higher for recipients of T-cell-depleted bone marrow compared with recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than 0.0001) and for patients who did not develop chronic graft-versus-host disease (95% CI, 50% to 60%) with patients who did (relative risk, 3.1; P less than 0.01). The probability of survival was lower for patients who developed moderate to severe acute graft-versus-host disease than for patients with no or mild acute graft-versus-host disease (relative risk, 3.7; P less than 0.0001), and in patients aged 20 or older than in younger patients (relative risk, 2.6; P less than 0.0002). Duration of disease before transplant was not associated with outcome. Bone marrow transplantation done in the chronic phase of chronic myelogenous leukemia offers some patients prolonged leukemia-free survival. The T-cell-depleted grafts are associated with an increased probability of relapse.     

Intensive chemotherapy in aggressive lymphomas: updated results of LNH- 80 protocol and prognostic factors affecting response and survival

One hundred patients with aggressive malignant lymphomas treated with the LNH-80 regimen were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. LNH- 80 consists of three intensive courses of adriamycin cyclophosphamide vindesine bleomycin (ACVB) followed by sequential consolidation and final intensification. Eighty-four patients went into complete remission (CR), eight had a partial response (PR), three failed to respond, and five died during induction. Twenty-three patients (27%) relapsed, in two of whom a prolonged second remission was obtained. Sixty-three patients are currently alive, two of them with disease. Four patients died in CR. Median survival and median freedom from relapse survival were not reached with a median follow-up of 4 1/2 years. Characteristics negatively associated with response in multivariate analysis were: poor performance status, bone marrow involvement, and two or more extranodal sites of disease. Duration of CR was associated with splenic involvement. Three characteristics were negatively associated with survival in multivariate analysis: age, high grade subtypes, and bone marrow involvement.     

Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study

The associations of cytogenetics with complete remission (CR) rates, overall survival (OS), and outcomes after CR were studied in 609 previously untreated AML patients younger than 56 years old in a clinical trial comparing 3 intensive postremission therapies: intensive chemotherapy, autologous transplantation (ABMT), or allogeneic bone marrow transplantation (alloBMT) from matched related donors. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes. CR rates varied significantly (P <.0001) among the 4 groups: favorable, 84% (95% confidence interval [CI], 77%-90%); intermediate, 76% (CI, 71%-81%); unfavorable, 55% (CI, 48%-63%); and unknown, 54% (CI, 33%-74%). There was similar significant heterogeneity of OS (P <.0001), with the estimated relative risk of death from any cause being 1.50 (CI, 1.10-2.05), 3. 33 (CI, 2.43-4.55), and 2.66 (CI, 1.59-4.45) for the intermediate, unfavorable, and unknown risk groups, respectively, compared with the favorable group. In multivariate analyses, the effects of cytogenetic risk status on CR rate and OS could not be explained by other patient or disease characteristics. Among postremission patients, survival from CR varied significantly among favorable, intermediate, and unfavorable groups (P =.0003), with significant evidence of interaction (P =.017) between the effects of treatment and cytogenetic risk status on survival. Patients with favorable cytogenetics did significantly better following ABMT and alloBMT than with chemotherapy alone, whereas patients with unfavorable cytogenetics did better with alloBMT. Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.     

Long-term survival and toxicity in small cell lung cancer. Expanded Southwest Oncology Group experience

The Southwest Oncology Group formed a database of 2,501 patients consecutively enrolled in small cell lung cancer (SCLC) trials since 1976. This report summarizes an analysis of this database to determine predictors of 2- and 5-year survival in limited stage disease (LD) and 1- and 2-year survival in extensive stage disease (ED). In addition, we analyzed the frequency of late recurrences, toxicity, and quality of life issues in the long-term survivors. For consecutive studies, greater than or equal to 2-year survival in LD were 15 percent, 21 percent, 28 percent, and 43 percent; 5-year survivals were 5 percent, 9 percent, 8 percent, and 20 percent. In ED, greater than or equal to 1-year survivals were 27 percent, 23 percent, 21 percent, and 42 percent; greater than or equal to 2-year survivals were 6 percent, 5 percent, 3 percent, and 19 percent. Using the logistic regression multivariate model, independent favorable predictors of 5-year survival for patients accrued to our older LD trials were normal lactate dehydrogenase (LDH) values and good performance status. Therapy as employed in these trials was not an independent factor. However, if patients enrolled on more recent trials were included, 2-year predictors could be assessed. Therapy with concurrent chemoradiotherapy and female gender then became additional independent favorable predictors. In ED, a single metastatic site and a normal LHH value were favorable predictors of survival beyond 1 year. The retrospective review of 63 patients with LD who survived at least 5 years found 33 asymptomatic patients with no recurrent disease; 6 with recurrent SCLC, 3 of whom died; 7 who died of non-cancer-related causes or unknown causes; 3 who died of secondary primary lung cancer; and 14 alive with persistent central nervous system symptoms and signs, possibly due to prophylactic brain radiation as given in the first 3 trials. No increased incidence of this syndrome has yet been observed in subsequent trials. For ED patients, 25 of 51 survivors greater than or equal to 2 years subsequently died of recurrent SCLC. The majority of the long-term survivors with ED (35 of 51) had either a single metastatic site or metastases limited to opposite side of the chest or regional nodes. Our multivariate models support the conclusion that aggressive combined modality, concurrent induction therapy, along with favorable prognostic variables, independently contribute to the improved long-term survival we have observed in LD. Longer follow-up is required to confirm that this improvement has occurred with less late toxicity.     

Prognostic factors in small cell lung cancer

In order to find out prognostic factors and treatment results in small cell lung cancer (SCLC), 40 patients diagnosed in one year period were prospectively analysed. Following history and physical examination, patients were grouped according to ECOG performance scale and underwent Chest X-ray and thoracic computerized tomography (CT). Complete blood count, biochemical analyses, tumor markers were taken. Abdominal USG or CT, bone scintigraphy, cranial CT or MRI and bone marrow biopsy were made for detection of metastases. Limited stage patients received chemotherapy and thoracic RT, whereas cases with extensive disease received chemotherapy. Nineteen cases had limited and 21 had extensive disease. When laboratory findings between 2 stages were compared, LDH, SGOT and GGT were significantly higher in extensive stage (p= 0.005, 0.015, 0.001, respectively). Overall median survival was 6 +/- 1 months, cumulative survival in 6 and 12 months were 39% and 20.72%, respectively. Median survival was 10 +/- 2 months in limited stage and 3 +/- 1 months in extensive stage, with a statististically significant difference. Univariate analyses showed that incresed LDH, CA15-3, GGT and SGOT levels, hipoproteinemia and poor performance scale were poor prognostic signs (p= 0.024, 0.032, 0.047, 0.013, 0.021 ve 0.013, respectively), however multivariate analyses revealed no significant difference. Other blood tests, pleural effusion, age, mediastinal lymph node metastases and weight loss had no prognostic effect. Stage was found to be progniostic factor with both univariate and multivariate analyses (p= 0.045).     

Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention

Veno-occlusive disease (VOD) of the liver is a complication observed particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is a polydeoxyribonucleotide with aptameric activity on endothelium. We evaluated in a retrospective analysis the efficacy of DF in pediatric patients developing hepatic VOD after HSCT.A total of 45 patients between 0.2 and 20 years (median age: 8.2 years) with hepatic VOD were treated with DF: 22 patients (49%) met risk criteria for severe or progressive disease and 23 (51%) for moderately severe and mild disease. The median duration of DF treatment was 17 days. In all, 34 patients (76%) achieved complete response (CR) with a survival rate of 64% at day 100. CR rate in patients with severe disease was 50% with long-term survival of 36%. The average DF dose in the CR group was 45 mg/kg/day and in the no responder (NR) group 27 mg/kg/day. The use of additional drugs besides DF to treat VOD made no difference in the outcome compared to DF alone. The average interval from diagnosis to start of DF was 1 day in the CR and 5.5 days in NR group. In multivariate analysis, early intervention remained the only significant factor for a CR.     

Low dose cytosine arabinoside in refractory anemia with excess of blasts in transformation

Summary Myelodysplastic syndromes (MDS) are heterogeneous diseases. Patients with blast counts of more than 20% of nucleated bone marrow cells have a high risk of short survival. We treated six patients with refractory anemia with excess of blast in transformation (RAEBiT) with low dose cytosine arabinoside (LD Ara-C). We had one partial remission (PR), surviving 16 weeks and two complete remissions (CR), surviving 22 and 55+ months. Myelosupression was dominant in all patients, but was not as serious as with conventional remission-induction treatments for leukemias. Bone marrow aplasia occurred in all responding patients, but a differentiation effect is possible too. Maintenance therapy with LD Ara-C may be important for the two long-lasting CR.     

Stages I and II diffuse large cell lymphomas: prognostic factors and long-term results with CHOP-bleo and radiotherapy.

One hundred forty-seven patients with Ann Arbor stages I and II diffuse large cell lymphoma (DLCL) were treated with combination chemotherapy consisting of cyclophosphamide, doxyrubicin, prednisone, and low-dose bleomycin (CHOP-Bleo) and involved-field radiation (IF XRT) between 1974 and 1984. A complete remission (CR) was attained by 54 of 57 patients with stage I disease and by 78 of 90 patients with stage II disease. Thirty-five patients had relapsing disease that occurred within 3 years in 31. The overall 10-year survival rate, counting all deaths, for patients with stage I was 72% as compared with 43% for patients with stage II (P less than .01). Determinate survival rates, censoring eight unrelated deaths, were similar to the overall survival rates: 77% and 51%, respectively. A multivariate analysis identified three independent prognostic factors: age, tumor extent, and serum lactic dehydrogenase (LDH) level. When the combined effect of tumor extent and LDH level were taken into consideration in the analysis, three risk groups for survival were identified. The best group, which consists of patients with minimum tumor and normal LDH levels, had a 10-year determinate survival of 79%. Patients with extensive tumors and elevated LDH levels had the poorest survival rate of 44%. An intermediate-risk group with a determinant survival of 62% was composed of patients with either extensive tumors or elevated LDH levels. These differences demonstrate the need to develop different treatment strategies based on risk factors for survival for patients with apparently localized Ann Arbor stages I/II DLCL.     

Allogeneic bone marrow transplantation for high risk acute lymphoblastic leukemia. Results from a single institution.

We present our experience with bone marrow transplantation (BMT) in 30 consecutive patients with high risk acute lymphoblastic leukemia. With a median follow-up of 4 years the disease-free survival (DFS) was 44% for the whole group, with a significant difference between patients in first or second complete remission (CR 1 and 2, as one group), compared with patients with more advanced disease (greater than CR2), 69.5% versus 15.4% (p less than 0.01). The main cause of BMT failure was leukemic relapse, with a relapse rate of 15% for patients in CR 1 and 2 and of 77% for patients with greater than CR2 (p less than 0.01). Among patients with active disease at BMT those who had 15% blast cells or less in the marrow fared better than those with more advanced disease or extramedullary relapse. Transplant-related death was 17%. Graft-versus-host disease (GVHD) was associated with an antileukemic effect; the DFS for patients with acute and/or chronic GVHD was better than for patients with no GVHD at all.     

The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation

One-hundred and five patients undergoing allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n = 61) and chronic myeloid leukaemia (n = 44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. There was a difference of +/- 18% between the nominal total dose of 990 cGy and the actual dose received as indicated by dosimetric recordings. While interstitial pneumonitis had minimal impact on survival (4%) there was a considerable difference in the incidence of relapses. The incidence of relapse was 55% versus 11% in patients receiving less or more than 990 cGy respectively and this had a major impact on survival (38% v. 74% at 7 years) since transplant-related mortality was comparable in the two groups. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%. 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GVHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced but a small reduction of the dose may significantly increase the risk of relapse.     

Intensive induction chemotherapy for small cell anaplastic carcinoma of the lung

The role of intensive induction chemotherapy in small cell cancer of the lung remains unclear. Twenty-eight newly diagnosed patients with small cell lung cancer were randomized to receive either high-dose or standard-dose cyclophosphamide, vincristine, and semustine in a trial where the dose of induction chemotherapy was the sole treatment variable. Complete responses (CR) were achieved in 57% of patients receiving high-dose therapy as compared to 21% of patients receiving standard-dose therapy (P less than 0.05). There was a higher rate of severe toxicity in the high-dose group (P less than 0.01). The overall median survival was not improved (36 weeks for the high-dose group vs 43 weeks for the standard-dose group); however, the median survival in patients achieving CR was prolonged (92 weeks for the high-dose group vs 50 weeks for the standard-dose group). These effects were most pronounced in patients with extensive disease; a CR after induction was achieved in five of nine patients treated with high doses but not in any of those treated with standard doses (P less than 0.05). A small group of patients appear to benefit by achieving a long-term remission with intensive induction chemotherapy, but this effect may be offset by increased morbidity.     

Chronic graft-versus-host disease after allogeneic bone marrow transplantation from an unrelated donor: incidence, risk factors and association with relapse. A report from the Japan Marrow Donor Program

Chronic graft-versus-host disease (GVHD) remains the major cause of late morbidity and mortality after allogeneic stem cell transplantation. We retrospectively analysed 2937 patients who underwent bone marrow transplantation from an unrelated donor (UR-BMT) facilitated by the Japan Marrow Donor Program (JMDP) and survived beyond day 100 after transplantation. The cumulative incidence of chronic GVHD (limited + extensive) or extensive chronic GVHD at 5 years post-transplant was 45.8% and 28.2%, respectively. On multivariate analysis, seven variables predicting chronic GVHD were identified: recipient age over 20 years, donor age over 30 years, primary diagnosis of chronic myeloid leukaemia, human leucocyte antigen (HLA)-A or -B mismatch, total body irradiation-containing regimen, platelet count not having reached 50 x 10(9)/l by day 100, and prior acute GVHD. Among 2609 patients with haematological malignancy, overall survival was significantly higher in patients with limited chronic GVHD but lower in patients with extensive chronic GVHD compared with those without chronic GVHD. The cumulative incidence of relapse among patients with limited or extensive chronic GVHD was significantly lower than that among patients without chronic GVHD. Our results suggest that limited chronic GVHD provides a survival benefit to patients with haematological malignancies by reducing the risk of relapse without increasing the risk of death from chronic GVHD.     

Pretreatment staging evaluation in small cell lung carcinoma. A new approach to medical decision making.

The real need for extensive staging at the time of diagnosis is discussed in regard to small cell lung carcinoma. We performed a decisional retrospective analysis on a series of 182 patients, based on three staging steps: the first step included physical examination and routine biologic tests. The second step consisted of liver ultrasonography and needle aspiration of any clinically detectable tumor mass, and the third step included bone marrow examination, radionuclide bone scan, thoracic, abdominal, and brain CT scan. A stepwise multivariate logistic regression performed on 11 variables considered in the first step shows that a four-parameter model can predict the spread of the disease (limited or extensive): weight loss, performance status, and elevated LDH or alkaline phosphatase levels. Limited disease can be predicted in two ways: (1) elevated LDH with normal alkaline phosphatases, no weight loss, and good performance status, or (2) normal LDH and alkaline phosphatases. In this series, 28 percent of patients can be predicted as having extensive disease and can be treated with chemotherapy alone without chest irradiation. After the second step, the probability of disease being extensive is only 25 percent, and only 84 (46.15 percent) patients would need to undergo the third step of staging procedures (brain CT scan, bone marrow aspiration and biopsy, radionuclide bone scan) with this method. We conclude that a multistep approach represents a simple staging method and offers the advantage of harmlessness and lower costs for patients not to be evaluated in prospective clinical trials.     

Allogeneic bone marrow tranplantation for young adult patients with newly diagnosed acute myeloid leukemia: HLA-Matched sibling donor availability does not improve treatment ouctome

In order to assess the place of HLA-identical allogeneic bone marrow transplantation (BMT) and to compare it to other post-induction therapies, we analyzed patient outcome in intention-to-treat based on the presence or not of an HLA-identical familial donor in young adults with de novo acute myeloid leukemia (AML) in first complete remission (CR). Between 1985 and 1998, 152 consecutive AML patients aged less than 41 years old, seen in our institution, were treated according to 3 different successive protocols (LYLAM85, LAM90, AML10). 144/152 patients entered our prospective study in which they were registered at time of diagnosis for presence or absence of HLA-identical donor and analyzed in intention-to-treat. In this study, 52 patients (36%), who had at least one identical sibling donor (group 1), were offered allogeneic BMT after CR achievement. The 92 patients without donor were allocated to group 2 and were assigned to receive chemotherapy or autologous transplantation as post-remission according to the protocol they were initially included in. Patients from both groups had similar disease characteristics at diagnosis. Karyotypes at diagnosis were defined as low risk (t(8;21) or t(15;17) or chromosome 16 abnormalities(, intermediate risk (normal karyotypes), or high risk (other abnormalities). Overall, 114/152 patients (75%) achieved a CR. Of the 144 eligible patients, 46/52 (88%) with a donor and 68/92 (74%) without a donor achieved a CR. The median follow-up duration of the 144 patients was 21.2 months. The relapse rate was higher in group 2 (56%) than in group 1 (31%). However, the overall survival was not different between patients with and without donor (median survival respectively at 16.7 months and 26.6 months with estimated survival at 5 years respectively at 32% and 34%). Thirty-four patients from group 1 (65%) were actually transplanted in first CR. The probability of 5-year survival for patients receiving effectively allogeneic BMT was 44% and was not significantly better than that of patients who did not. In univariate as in multivariate analysis, karyotypic status was the main prognostic factor for CR achievement (p = 0.002), CR duration (p < 0.0001), and overall survival (p < 0.0001). There were no significant differences between group 1 and group 2 when survivals were compared with adjustment for karyotypes.We conclude that the availability of an HLA-identical sibling donor did not confer any prognostic advantage in terms of outcome for young adults with AML in first CR. These results make allogeneic BMT process questionable as systemic post-remission therapy in patients with an HLA-identical familial donor.     

Pretreatment tumor mass, cell kinetics, and prognosis in multiple myeloma

One-hundred fifty patients with multiple (plasma cell) myeloma had pretreatment tumor mass staging, and 79 also had measurement of the pretreatment labeling index (LI%). There were clear differences in survival by pretreatment stage of disease. The pretreatment LI% of bone marrow plasma cells was an independent prognostic factor both in single factor and multivariate regression analyses, including myeloma stage (p less than 0.02). Other important prognostic factors (multivariate) included performance status, serum creatinine, presence of Bence Jones protein, age, and kappa/lambda subtype. A LI% of less than 1% was associated with long survival in each patient group. Patients with benign gammopathy had excellent survival and very low labeling indices. A pretreatment LI% of greater than 3% in high cell mass patients with a high total number of DNA synthesizing cells (S) conferred a very poor prognosis (p = 0.002). This subgroup of patients with high S values also had a high incidence of central nervous system relapse (27%), Bence Jones proteinuria, and elevated serum uric acid levels. We conclude that the pretreatment labeling index provides helpful prognostic information in addition to tumor mass staging.     

Risk of relapse and clinico-pathological features in 103 patients with diffuse large-cell lymphoma in complete response after first-line treatment

Abstract: Patients with diffuse large-cell lymphoma (DLCL) achieve a complete response (CR) in most cases, but at least one-third of them eventually relapse. Such an event occurs most frequently within 2 yr from CR achievement. The aim of the present study was to analyse the risk and pattern of relapse of patients with DLCL in CR. One hundred and three patients with DLCL (53 male/50 female; median age: 55 yr) in CR after doxorubicin-containing first-line treatments were included in the study. Main clinicobiological characteristics at diagnosis and at relapse were analysed. Uni- and multivariate studies were performed. Forty-one patients (40%) eventually relapsed, in 27 cases within 2 yr from CR and 14 thereafter. Histological subtype was the same at diagnosis and at relapse in all the early relapsing patients and in 8 of 10 late relapsing patients with available biopsy. The most important variables at diagnosis for predicting relapse were advanced stage (p < 0.01) and bone marrow infiltration (p = 0.05), with stage (I–II vs. III–IV) (p = 0.009; relative risk = 2.28) being the only predictive variable in the multivariate analysis. No differences were found according to the treatment given. The second CR rate obtained in the late relapsing patients after salvage therapies was higher that in early relapsing (50% vs. 37%). Median survival from relapse was 1.4 yr for patients early relapsing and it was not achieved for those with late relapses (p = 0.09). Late relapse is a quite common event in DLCL lymphomas, with those patients achieving more frequently a second CR and having better survival than early relapsed patients.     

Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry

Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML) received haematopoietic stem cell transplants (SCT) from related (n = 132) or unrelated (n = 40) donors at four Austrian transplant centres and their results were reported to the Austrian Stem Cell Transplantation Registry. Conditioning for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%) patients. Graft-versus-host disease (GVHD) prophylaxis was with standard cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow-up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related mortality (TRM) identified four variables associated with a lower risk: disease status of first complete remission (CR) at SCT, patient age of 45 years and younger, transplant performed during or after 1995, and lack of acute GVHD. Variables associated with significantly improved leukaemia-free survival were: bone marrow as the stem cell source, disease status of first CR at SCT, and occurrence of chronic GVHD. In multivariate analysis, transplantation performed during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and lack of acute GVHD grades III to IV were associated with increased overall survival. Based on these analyses, options for the improvement of results obtained with allogeneic SCT in patients with AML could be defined.     

Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia

The importance of banded chromosome analyses in predicting long-term outcome in acute lymphoblastic leukemia (ALL) was evaluated in this follow-up study of 329 patients from the Third International Workshop on Chromosomes in Leukemia. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, translocations involving 8q24,t(4;11), 14q+, 6q-] or, in the remaining cases, modal number [less than 46, 46, 47 to 50, greater than 50]. Achievement and duration of complete remission (CR) and survival differed among chromosome groups (P less than .0001). Karyotype was an independent prognostic factor for duration of first CR and survival, even when age, initial leukocyte count (WBC), French-American-British (FAB) type, and immunologic phenotype were considered. Among adults, prolonged remission and survival were uncommon in all chromosome groups. Only in the normal karyotype group was median survival even two years. Among children, striking differences in long-term remission and survival were seen depending upon karyotype. Children in the greater than 50 group did best, with 70% remaining in first CR for a median duration in excess of five years. Children in the 47-50, 6q-, and normal karyotype groups also had prolonged survivals. In contrast, certain translocations [t(9;22)(q34;q11), t(4;11)(q21;q14-23), t(8;14)(q24;q32)] identified children who had short survivals, even in the presence of favorable prognostic factors including a low WBC, L1 morphology, and non-T, non-B immunologic phenotype. We conclude that chromosome analysis is required at diagnosis in patients with ALL, and that children with these specific translocations should be managed as having high-risk ALL.