Two cycles of escalated BEACOPP followed by four cycles of ABVD utilizing early-interim PET/CT scan is an effective regimen for advanced high-risk Hodgkin's lymphoma.

BACKGROUND: Escalated combination therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (escBEACOPP) regimen is superior to cyclophosphamide, vincristine, procarbazine and prednisone alternating with doxorubicin, bleomycin, vinblastine and dacarbazine (COPP-ABVD) for advanced-stage Hodgkin's lymphoma (HL) patients. However, the original schedule of eight cycles of escBEACOPP was associated with significant toxicity. This study was conducted in an attempt to reduce the toxicity of the original schedule, while attempting to preserve improved initial tumor control. PATIENTS AND METHODS: Forty-five newly diagnosed patients with advanced-stage HL and International Prognostic Score > or = 3 received two initial cycles of escBEACOPP and then were evaluated by positron emission tomography (PET)/computed tomography scan. If a good imaging response was obtained, they were treated by four cycles of ABVD. RESULTS: Following the first two cycles of escBEACOPP, the overall response was 100% and at the end of all therapy, 40 (89%) patients were in complete response (disappearance of all clinical evidence of disease and PET negativity), three (7%) in partial response (PET-positive residual lesions and a size reduction of the majority of large masses by >50%), while two (4%) had progressive disease. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival at 4 years were 78% and 95%, respectively. The 4-year PFS for early PET-negative patients (n = 31) and early PET-positive patients (n = 13) were 87% and 53%, respectively (P = 0.01). CONCLUSIONS: These data indicate that combined escBEACOPP-ABVD may improve the outcome in patients with high-risk advanced HL. The potential benefit of early-interim PET activity as a guide to continuing therapy in these patients merits further study in the future.

Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma.

Allogeneic SCT is an effective therapy for lymphoma. Reduced-intensity conditioning (RIC) reduces non-relapse mortality (NRM) associated with myeloablative conditioning but relapse rates are high when performed in active disease. This study was designed to explore the safety and outcome of ibritumomab tiuxetan (Zevalin) combined with RIC in patients with advanced lymphoma. The study included 12 patients, median age 54 years (37-62), with a median of four prior treatments (2-6) and active disease documented on PET-CT. Zevalin 0.4 mCi/kg was given on day -14 and fludarabine combined with BU (n=6) or melphalan (n=6) was started on day -6. GVHD prevention was tapered 3 months after SCT to augment the graft-versus-lymphoma effect. All patients engrafted, a median of 14 days after SCT. Eighty-three percent achieved CR/PR. With a median follow-up of 21 months (12-37), 2-year PFS is 33%. Only three patients relapsed; cumulative incidence 25%. NRM was 42%, predominantly due to acute GVHD. Zevalin-RIC is feasible with consistent engraftment, acceptable organ toxicity, but high rates of acute GVHD. The low incidence of relapse suggests augmented anti-lymphoma effect. Zevalin-RIC merits further study. Better results may be achieved in patients earlier in disease course and with longer duration of immune-suppression.

Drug-induced erythrocyte membrane internalization.

In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of (37)Co-labeled vitamin B(12) and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the noninternalized label is removed by washing and trypsin treatment. The residual radioactivity represents trapped label and can be used to measure the extent of membrane internalization. Using this method, it was found that in addition to primaquine, a group of membrane-active drugs, specifically hydrocortisone, vinblastine, and chlorpromazine can induce membrane internalization in erythrocytes. This is a metabolic process dependent on drug concentration, temperature, and pH. Vacuole formation by all agents tested can be blocked by prior depletion of endogenous substrates or by poisoning the erythrocytes with sodium fluoride and sulfhydryl blocking agents. This phenomenon resembles in some respects the previously reported membrane internalization of energized erythrocyte ghosts. It is suggested that membrane internalization is dependent on an ATP-energized state and is influenced by the balance between the concentrations of magnesium and calcium in the membrane. This study provides a basis for proposing a unifying concept of the action of some membrane-active drugs, and for considering the role of erythrocyte membrane internalization in pathophysiologic events.

Graft-versus-leukemia in chronic lymphocytic leukemia.

Immune-mediated anti-leukemia effects, often termed graft-versus-leukemia (GvL), operate after bone marrow or blood cell transplants for acute lymphoblastic leukemia, acute myelogenous leukemia and chronic myelogenous leukemia. Sometimes the magnitude of this anti-leukemia effect exceeds that of high-dose anti-leukemia drugs and radiation and can result in leukemia cure. We analyzed leukemia relapse data after transplants for chronic lymphocytic leukemia (CLL) in this context. These data support the notion of a strong GvL effect in CLL. However, as most of these data are from studies of allotransplants, it is uncertain whether GvL operates in settings where the anti-leukemia effector cells and target CLL cells are genetically identical except for leukemia-related mutations. It is also uncertain whether GvL is distinct from GvHD. These potential limitations have important implications on whether immune therapy of CLL will work in non-allotransplant settings.

Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity.

Allogeneic stem-cell transplantation (SCT) with both myeloablative and reduced-intensity conditioning (RIC) is an effective therapy in AML/MDS. However, the relative merits of each may differ in different settings. To define the role of dose intensity, we analyzed SCT outcomes of 112 consecutive patients with AML/MDS. A total of 45 patients met eligibility criteria for standard myeloablative conditioning and were given intravenous-busulfan (12.8 mg/kg) and cyclophosphamide (ivBuCy). A total of 67 noneligible patients were given RIC with fludarabine and intravenous-busulfan (6.4 mg/kg, FB2, n=41) or a modified myeloablative regimen with fludarabine and myeloablative doses of intravenous-busulfan (12.8 mg/kg, FB4, n=26). The overall survival (OS) at 2 years was 50, 49 and 47% after ivBuCy, FB4 and FB2, respectively (P=NS). Nonrelapse mortality was higher after ivBuCy, 22 vs 8% (P=0.05), but relapse rates were lower. Active disease at SCT was the most significant predictor of reduced survival in multivariable analysis (HR 4.5, P=0.0001). Myeloablative and RIC regimens had similar outcomes when leukemia was in remission at SCT; however, patients with active disease could only be salvaged by myeloablative conditioning. Among the latter, OS was 45% after ivBuCy but no FB2 recipient survived (P=0.02). Patients with active disease, ineligible for standard myeloablation, could tolerate modified myeloablation well; however, long-term outcome cannot be determined yet.

Hematopoietic stem-cell transplantation from unrelated donors in elderly patients (age >55 years) with hematologic malignancies: older age is no longer a contraindication when using reduced intensity conditioning.

Allogeneic stem cell transplantation (SCT) is a potentially curative approach for patients with hematological malignancies. Reduced-intensity conditioning regimens allow SCT in elderly patients; however, there are only limited data on the feasibility and outcomes of unrelated donor SCT in these patients. In this study, we analyzed, retrospectively, data of 36 patients with various hematological malignancies and median age 58 years (range, 55-66), who were given unrelated donor SCT after reduced-intensity conditioning. The preparative regimen consisted of fludarabine combined with oral busulfan (8 mg/kg, n=8), intravenous busulfan (6.4 mg/kg, n=11), treosulfan (30 g/m(2), n=5) or melphalan (100-150 mg/m(2), n=12). Patients were also given serotherapy, ATG (n=32), or alemtuzumab (n=4). The probabilities of overall survival, disease-free survival, and nonrelapse mortality at 1 year after SCT were 52, 43, and 39%, respectively. Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD occurred in 31 and 45%, respectively. Multivariable analysis determined that survival rates were higher in patients with chemosensitive disease (HR 4.5), and patients conditioned with intravenous busulfan or treosulfan (HR 3.9). Unrelated donor SCT is feasible in elderly patients, with outcomes that are similar to younger patients. Favorable outcome was observed in patients with myeloid malignancies, and those transplanted in remission and early in the course of disease. Age alone should not be considered a contraindication to unrelated donor SCT.

Fluidity difference of membrane lipids in human normal and leukemic lymphocytes as controlled by serum components.

Lymphocytes isolated from the peripheral blood of patients with chronic lymphatic leukemia and from normal healthy donors were analyzed for fluidity of membrane lipids. The degree of lipid fluidity in normal and leukemic lymphocytes was quantitatively monitored by a method based on fluorescence polarization analysis of a fluorescent probe that is embedded in lipid regions of cellular membrances. The present studies were performed on lymphocytes isolated from 26 blood samples from 16 patients with chronic lymphatic leukemia and 36 blood samples from 36 normal health donors. A signifcant increase in the degree of fluidity of membrane lipids was found in lymphocytes isolated from leukemic patients as compared to that found for lymphocytes isolated from healthy donors. In vitro incubation of leukemic lymphocytes in normal serum resulted in a decrease in the fluidity of cellular membranes, whereas incubation of normal lymphocytes in leukemic serum resulted in an increase in the fluidity of membrane lipids. These observations suggest that normal and leukemic lymphocytes can be quantitatively characterized by monitoring degree of fluidity of cellular membrane lipids and that the fluidity difference between normal and leukemic lymphocytes is controlled by components in the blood serum.

More than two immunoglobulin heavy chain J region genes in the majority of infant leukemia.

Congenital and infant leukemia are rare conditions associated with a very poor prognosis due to the high frequency of adverse clinical and laboratory parameters. As the occurrence of multiple immunoglobulin heavy chain hybridization band in childhood leukemia has been associated with poor prognosis, we studied whether it was present in this type of leukemia as well. Seven cases were examined, 4 of them less than 7 months of age. The immunophenotype was lymphoid in 5 and hybrid in 2. Most had abnormal karyotypes. In 5 of the 7, including all with congenital leukemia, an immunoglobulin heavy chain J region multiband pattern was found by Southern blot. The multiband pattern, whether primary or due to clonal evolution, seems to be associated with poor prognosis.

Imatinib mesylate (STI571) in preparation for allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusions in patients with Philadelphia-positive acute leukemias.

Chronic myeloid leukemia in blast crisis (BC) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) are associated with extremely poor outcome. Allogeneic transplantation during BC or active leukemia is most often unsuccessful due to high-rates of both treatment-related complications and relapse. Long-term results are significantly better if a second chronic phase or remission can be achieved prior to transplantation. Similarly, DLI given for the treatment of post-transplant relapse is more successful when given during a second remission. In this study we report our results with a previously unreported approach consisting of short-term treatment with imatinib mesylate (formerly, STI571) to induce or maintain remission, followed by allogeneic transplantation or DLI and the impact on transplantation/DLI outcome. Sixteen patients were treated either in preparation for transplantation (n = 12), for DLI (n = 1), or for both (n = 3). Ten had CML in BC; seven myeloid and three lymphoid BC. Six patients had Ph(+) ALL. The donors were matched unrelated (n = 9), matched siblings (n = 5) or haplo-identical (n = 2). Eleven of 15 patients given imatinib pre-transplant were transplanted in complete hematologic response. Engraftment and GVHD rates were not different from expected. Seven patients had grade II-III hepatic toxicity after transplantation. After a median follow-up of 10 months (range, 3-16 months) six remain alive, two after further therapy. The 1-year survival rate was 25%. Four patients were given imatinib prior to DLI, all had complete response. Two remain in remission >6 months from relapse. In conclusion, treatment with imatinib allows transplantation in a more favorable status or maintaining remission with low toxicity until transplantation is feasible. Pre-transplant imatinib seems safe and not associated with excess post-transplant complications. Imatinib may have substantial activity in combination with DLI. Further study of a larger group of patients is required to assess the impact on long-term outcome and the role of post-transplant imatinib in controlling residual disease.

In vivo clonal evolution of pre-B to B-cell acute lymphoblastic leukemia in childhood.

Two cases are described that provide further evidence for clonal evolution in pre-B-cell acute lymphoblastic leukemia. Two infants, whose lymphoblasts at diagnosis were morphologically subtyped as L1 and immunophenotyped as HLA DR+, CD19+, CD10+/- and C mu-, were induced and maintained in remission. One child relapsed 6 months after initiation of therapy. This time his lymphoblasts had L3 morphology and immunophenotyping demonstrated the appearance of surface immunoglobulins. The second child relapsed 18 months after initiation of therapy with a lymphomatous picture. He also had peripheral and bone marrow blasts with L3 morphology and surface immunoglobulins. A lymph node biopsy showed diffuse small non-cleaved lymphoma with a 'starry sky' appearance compatible with Burkitt's lymphoma. Only one case with a similar clonal evolution has been reported in the literature, but no surface immunoglobulins were demonstrated. The significance of clonal evolution in these cases and its potential practical implications are discussed.

A search for bcl1, bcl2, and c-myc oncogene rearrangements in chronic lymphocytic leukemia.

Three cellular or putative oncogenes: c-myc, bcl1, and bcl2 were previously found to be rearranged in some B cell malignancies due to chromosomal translocations. Data concerning the role of such genetic rearrangements in B-CLL are very scanty and limited to few cases in which bcl1 rearrangements were found. We studied DNA samples from 38 cases of B-CLL by Southern blot technique in order to find out the existence and frequency of such events. No bcl1 or bcl2 rearrangements were found in any of the studied cases; thus, involvement of these genes in CLL must be rare. In one patient who had an aggressive and resistant disease, c-myc rearrangement was found.

Evaluation of an intervention aimed at reducing inappropriate use of preoperative blood coagulation tests.

A multiphase intervention trial based on education, implementation of criteria, and restriction, aimed at modifying the established clinical policy of mandatory preoperative screening for coagulation abnormalities, was carried out on five surgical wards of a general hospital. The education period did not influence the ordering of partial thromboplastin time tests, despite a significant posteducational change in surgeons' attitudes. In contrast, administrative restriction of coagulation test orders led to a 50% decline on four of the five study wards. We conclude that an educational intervention followed by administrative restriction may be considered an acceptable means of overcoming clinician reluctance to change well-established but redundant clinical policy.

Effect of alpha interferon on growth of leukemic and normal hematopoietic progenitors. Synergism with H2 histamine receptor antagonists.

We studied whether the histamine H2 receptor antagonist, cimetidine, potentiates antiproliferative effects of recombinant alpha interferon (IFN alpha) on in vitro clonal growth of certain normal and malignant hematopoietic cells. Cimetidine alone, at therapeutic serum concentrations, was not inhibitory to the cells studied. IFN alpha alone inhibited the growth of HL-60 leukemic cells only at concentrations greater than 1000 U/ml, whereas with cimetidine, inhibition was seen at greater than 1 U/ml of IFN alpha. The enhancing effect of cimetidine on IFN alpha inhibition of clonal growth was neutralized by histamine and was not seen with histamine H1 receptor antagonist. In HL-60 cells, cimetidine also increased the enzymatic activity of (2'-5')-oligoadenylate synthetase, induced by IFN alpha. The combination of cimetidine and IFN alpha had a synergistic inhibitory effect on the growth of leukemic granulocyte-macrophage colony-forming units (CFU-GM) from chronic myeloid leukemia patients, normal CFU-GM, and normal erythroid burst-forming unit (BFU-E) progenitors. These data suggest that cimetidine may play a role in overcoming resistance to IFN alpha therapy in leukemia, but may also increase IFN alpha hematopoietic toxicity.

Infectious agents and environmental factors in lymphoid malignancies.

A strong association was found to exist between patterns of lymphoid malignancies and socioeconomic status. B-cell lymphomas and T-acute lymphoblastic leukemia are much more prevalent in developing countries where the chances of acquiring infections especially at a younger age are high. B-cell precursor acute lymphatic leukemia, however, are much more prevalent in the Western world. Many infectious agents are associated with lymphatic malignancies. Epstein-Barr virus is involved in African Burkitt's lymphoma, human immunodeficiency virus-related Burkitt's lymphoma, lymphoproliferative syndrome post-transplantation, and Hodgkin's disease. Other infectious agents which may play a role in lymphoproliferative disorders are human immunodeficiency virus in acquired immune deficiency syndrome-associated lymphoma, human T-lymphotropic virus in adult T-cell lymphoma, Helicobacter pylori in mucosa-associated lymphoid tissue lymphoma, theileriosis in lymphoproliferative syndrome in cattle, Avian leukosis virus in chicken bursal lymphoma, and possibly a bacterial infection in immunoproliferative small intestine disease, potentially reversed by antibiotic therapy. The association between infectious agents and hematologic malignancies may be explained by the creation of large populations of activated cells followed by higher occurrences of 'genetic accidents'. This theory may be reinforced in at least some malignancies with the existence of viral proteins which either have complex relationships with key cellular gene products like p53 and Rb which have roles in cell cycle control, or share common motifs with bc1-2, therefore operating as anti-apoptotic elements. Whenever these genes are deranged, cell deoxysibonucleic acid repair or apoptosis are no longer possible, thereby creating a state of genome instability, increased acquisition of mistakes, and increased chances for malignant transformation.

The epidemiology of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma in Israel between 1976 and 1981.

n epidemiologic survey of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) occurring in Israel, Judea, Samaria and the Gaza Strip between the years 1976 and 1981, revealed 205 cases of ALL and 69 of NHL. The mean annual incidence of lymphatic malignancies was 3.1/10(5) in the Israeli Jews, 2.3/10(5) in the Israeli Arabs and 2.5/10(5) in the Gaza Strip. In the Jewish population there was a peak in the incidence of lymphatic malignancies at the 2-5 years age group, while in the Israeli Arabs this was less prominent. There were no significant differences in the incidence or type of lymphatic malignancies in the various Jewish or Arab groups but there was a trend for a high leukemia to lymphoma ratio (LLR) in the patients from the Gaza Strip. A relatively higher LLR was observed in families of a high socioeconomic status, but it did not reach statistical significance. T-cell ALL comprised about a third of the typed ALL cases. A high proportion of the patients with ALL belonged to the high-risk category: 46% of the Jewish children and 76% of the Gaza Strip children. White blood cell count above 100,000/mm3 were found at presentation in 36.7% of the Gaza Strip patients but only in 9.4% of the Jewish patients. In spite of that, the survival at 4 years of the Jewish and Arab patients was similar. However, the patients with T-cell ALL had a significantly worse survival than the standard risk or the non-T high-risk group: 43.3 +/- 9.7, 66.6 +/- 7.1 and 63.6 +/- 10.4%, respectively. Compared to a previous study conducted in this country in the sixties it appears that the epidemiologic differences that were observed at that time between the various Jewish ethnic groups have practically disappeared.

T-cell acute lymphoblastic leukemia in Israel: clinical and laboratory features.

T-cell acute lymphoblastic leukemia (ALL) comprises a third of the cases of childhood ALL in Israel. This high proportion of T-ALL is most probably due to a deficiency in pre-B/common ALL. The T-ALL patients had significantly worse 4-yr survival compared to standard risk or non-T high risk patients. In view of these special epidemiologic and clinical features a study of the immunophenotype of all consecutive cases of T-ALL and T-non Hodgkin's lymphoma (NHL) observed in our medical center was performed. Twenty-eight ALL and 3 NHL patients were studied and their cells characterized using a panel of monoclonal antibodies, TdT reactivity and E-rosette formation. Assays of the activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (NP) were also performed. Based on the surface antigen expression, the tumor cells could be classified into one of the three known developmental stages of T cells. It was found that the immunophenotype of the T-ALL cases in Israel was similar to that observed in other countries. Considerable heterogeneity of surface antigen expression was found and in a number of cases the phenotype analysis was not easily reconciled with models of T-cell ontogeny. The activities of ADA and NP were correlated with the developmental stage, as defined by the surface antigenic expression. Contrary to observations on normal T-cells, where ADA activity decreases and NP activity increases as T-cells mature and differentiate, this was not found in the malignant T cells. These findings as well as the existence of atypical immunophenotypes suggest that the leukemic T cell has an abnormal gene expression.

The MACOP-B and VACOP-B combination chemotherapy for young patients with intermediate-grade non-Hodgkin's lymphoma.

Since the early 1970s, three generations of combination chemotherapy for intermediate-grade non-Hodgkin's lymphomas (NHL) have been developed. One of the third-generation regimens is MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). The VACOP-B regimen is a modification of MACOP-B in which methotrexate is omitted and etoposide is added. This study assesses treatment outcome using the MACOP-B and VACOP-B combination chemotherapy in a population of young patients with intermediate-grade NHL treated in a single tertiary hematological center. The files of 45 patients aged 18-55 who were diagnosed as having intermediate-grade NHL (working formulation types F-H) and treated between January 1986 and March 1994 were reviewed. Treatment response, overall survival, disease-free survival and treatment toxicity were determined. The predictive value of the age-adjusted international prognostic index was also assessed. Median follow-up was 80 months in the MACOP-B group and 29 months in the VACOP-B group. The complete response rate was 71% (95% confidence interval CI: 58-84), 4-year overall survival was 74 +/- 7% and 4-year disease-free survival was 79 +/- 8%. No toxicity-related deaths were observed. The main adverse effects were WHO grade 3 or 4 neutropenia (51%), anemia (24%) and mucositis (20%). Only the CR rate was correlated with the Age-Adjusted International Prognostic Index. Mean relative dose intensity was high (95.7%, 95%) CI: 91.7-99.7) and had no correlation with treatment outcome. The MACOP-B and VACOP-B combination chemotherapy regimens were found to be effective and minimally toxic for young patients up to 55 years old with intermediate-grade NHL.

Acute lymphoblastic leukemia subtypes in Israel: the Sheba medical center experience.

During the period from 1978 to 1981, 52 patients with ALL were diagnosed and treated at the Chaim Sheba Medical Center. Using standard cell markers to subtype the blasts, 49 of the patients could be classified: 16 were found to be T-cell ALL, 10 common ALL, five null ALL, four pre-B and 14 were partially characterized as non-B, non-T. Analysis of the series revealed two distinctive features: high prevalence (30%) of T-cell ALL among both Jews and Arabs and a high proportion, two-thirds, of high risk patients due to high initial WBC counts, unfavourable age or T-cell characteristics. The minimal incidence of ALL among the Gaza Strip Arab children during the study period is 4:100,000, which is close to the incidence in the Western world. During previous years the leukemia incidence in the Gaza Strip was very low while the most common lymphatic malignancies were Burkitt tumor and other non-Hodgkin lymphomas.

Salvage therapy of refractory and relapsed acute leukemia with high dose mitoxantrone and high dose cytarabine.

We have assessed the outcome of 66 refractory and relapsed acute leukemia patients treated with high dose mitoxantrone and cytarabine. Therapy consisted of a total dose of 40-60 mg/m2 mitoxantrone and 3 g/m2 of cytarabine daily on 5 consecutive days. A total of 28 patients were treated for primary resistant and 38 patients for early or late relapsed leukemia. A total of 35 patients achieved CR. Four patients died during the induction course. Toxicity was acceptable and comparable to other salvage regimens. The median disease-free and overall survivals were 4 and 6 months, respectively. Although this regimen is effective in achieving remission in refractory leukemia, its duration is short.

Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia.

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% CI 11.2-23.1 months) and a 2 year survival of 34.3 +/- 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% CI, lower limit 29.8 months) and a 2 year survival of 71.6 +/- 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 +/- 6.6% in the IDAC group and 67.3 +/- 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 +/- 10.8% versus 23.5 +/- 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 +/- 15.78 versus 44.4 +/- 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.