ICE Protocol Research Articles

Primary liver lymphoma (PLL) with isolated CNS relapse

Background : Primary liver lymphoma (PLL) is a rare disease. Patients usually present with abdominal problems and liver mass without any extrahepatic tumor. PLL usually responds well to chemotherapy, while chemotherapy±radiation is the standard treatment of choice. Case report : A 42 year-old man was presented because of abdominal pain, 8.5kg weight loss and fever for 3 months. There was not lymphadenopathy, splenomegaly, abdominal mass or hepatomegaly in physical examination. A computed tomography (CT) scan of the abdomen disclosed multiple large liver masses without adenopathy. Patient responded well to CHOP chemotherapy regimen. Three months later, he was visited because of headache, dizziness and convulsion. A brain CT scan showed a mass in brain. He was treated by brain radiation plus intrathecal injection of methotrexate (MTX) (15mg) followed by 6 cycles of ICE protocol. Conclusion : PLL is a rare disease that responds well to multi-agent chemotherapy. CNS metastasis should be considered in the affected patients.

Feasibility of high-dose chemotherapy (HDCT) with doble autologous stem cell transplantation (ASCT) for Ewing and soft tissue sarcomas

21501 Background: To improve long-term outcome of metastatic sarcoma patients (pts), we started a tandem ASCT program in compassionate use. Its feasibility is analyzed. Methods: From January/2004 to April/2007, 11 pts (8 males, age 29 [19 - 51] years) were included: 7 Ewing, 2 rabdomyosarcoma, 1 sinovial and 1 leiomyosarcoma. Patients included in the program were those with CR or PR after conventional chemotherapy (CT). Median treatment lines before transplant was 1 (1–3). Conditioning regimen for both ASCTs was ICE protocol (HDCT) (ifosfamide 2,500 mg/m2 iv × 4 d, carboplatin 360 mg/m2 iv × 4 d., etoposide 310 mg/m2 iv × 4 d.). A minimum number of 4 × 106 CD34+/kg cels were collected. Results: 5 pts were in CR, 5 in PR just before ASCT. 1 pt that achieved a PR after CT, presented with an early progression just before the first ASCT. All pts underwent the first procedure. Post-transplant toxicity: grade (G) 4 neutropenia: (11d [7d-14d]), G4 thrombocytopenia: (7.7d [4–12]), G 3–4 gastrointestinal (GI) toxicity in 6 (54%) and severe venooclusive disease in 2 (18%) pts. All pts developed neutropenic fever. Two pts (18%) died from transplant related mortality (TRM). 3 other pts (27%) didn't proceed to 2nd intensive course due to early progression after first ASCT. Time interval between procedures was 3.6 (2–7) months. Second ASCT toxicity was: neutropenia G IV 11.5 (9–14) d and thrombocytopenia G4 5.8 (2–14) d. One pt (16%) developed G3 GI toxicity. TRM was 0%. With a median follow-up for all pts of 14.5 (1–35) months after the first transplant, 4 are alive (36%), 1 in CR, 3 in PR and 7 are death (63%). Conclusions: This tandem procedure is feasible but rather toxic: G 3–4 GI toxicity are higher than expected as well as TRM. Progression rate after the first ASCT procedure is not negligible. Other options should be sought for this bad-prognosis pts. No significant financial relationships to disclose.

Clinical Presentation, Treatment Response and Survival in Adult Acute Biphenotypic Leukemia: Single Centre Experience.

Background: Acute leukemia is classified as lymphoid or myeloid depends on antigen expression. Knowledge about acute biphenotopic leukemia (BAL) is limited; both in terms of clinical and biological presentation and also in regard to treatment outcome. Hereby we are completing the work done by our group which looked at the laboratory features of BAL by reviewing the clinical presentation and response to different chemotherapy protocols used at our institute for treatment of patients with BAL to estimate over all survival.Methods: Out of 478 adult patients with acute leukemia, we analyzed 15(3.1%) cases classified as BAL according to EGIL score system. Clinical data were collected retrospectively and analyzed. Five different chemotherapy protocols had been used. Six(40%) patients had received VCEPM (Vincristine 1.4mg/m2 x 4 doses, Cyclophosphamide 600mg/ m2 , Etoposide 100mg m2 daily for 5 doses, Prednisone 60mg/m2 for28 days). Four (27%)cases had received 1423 KFSH protocol (Cyclophosphamide 1200mg/m 2 x 1 dose, Daunorubicin 45mg/m2 for 3 doses, Vincristine 1.4mg/m2 once every week x 4 doses, Prednisone 60mg/m2 for 21 days, L-Asparaginase 6000 iu/m 2 every 3 days x 6 doses). Standard ICE protocol was used for induction in 3 cases and in 2 patients modified St Jude protocol (Vincristine 1.5mg/m 2 once every week x 4 doses, Daunomycin 25mg/m2 once every week x 2 doses, Prednisone 40mg/m 2 daily for 25 dose, L-Asparaginase 10000u/m 2 every 3 days for 6 doses, Etoposide 300mg/m 2 every 4 days x 3 doses and Cytarapin 300mg/m 2 every 4 days x 3 doses).Results: We had 11 males and 4 females with mean WBC count on presentation of 74.7 x 109/L.Chromosomal karyotype was done for all except one, 4(29%) were normal and 8(53%) had complex karyotype Of all patients with BAL leukemia, 4(27%), 8(53%) and 10(67%) had hepatomegaly,splenomegaly and lymphadenopathy respectively. Initial evaluation done on D14 post chemotherapy revealed evidence of residual leukemia (> 5% blasts) in 1 out of 6 patients treated with VCEPM and 7 out of the other 9 patients received different other protocols. Out of the eight patients with residual leukemia, 4 had received salvage chemotherapy with FA (Fludarabine 30mg/ m2, Cytarabine2mg/ m2 x 5doses) and 2 had received MEC (Mitoxantrone 6mg/ m2 , Etopside 80mg/ m2, Cytarabine1mg/ m 2 x 6 doses) and one received modified St Jude while one underwent for SCT. ALL except one had achieved CR. Total of 10(66%) underwent SCT in CR. Although there were 9 (60%) died during the follow up, the OS at two years was (50%).Conclusion: Adult BAL is an aggressive disease that is associated with complex karyotype with poor response to single lineage treatment. The use of hybrid drugs (VCEPM like) that are effective for lymphoid and myeloid leukemia improve the respond. [Display omitted]

A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine

AbstractThe value of administering sequential courses of chemotherapy containing high-dose cytarabine in both induction and consolidation therapy for acute myeloid leukemia (AML) has not been assessed in a prospective randomized trial. Two hundred ninety-two AML patients aged 15 to 60 years were enrolled in the Australasian Leukaemia and Lymphoma Group (ALLG) AML trial number 7 (M7) protocol to evaluate this question. All received induction therapy with the ICE protocol (idarubicin 9 mg/m2 × 3; cytarabine 3 g/m2 twice a day on days 1, 3, 5, 7; etoposide 75 mg/m2 × 7). Complete remission was achieved in 234 (80%) patients. Two hundred two patients in remission were then randomized to either a further identical cycle of ICE or 2 attenuated courses (cytarabine 100 mg/m2 daily × 5, idarubicin × 2, etoposide × 5 [IcE]). ICE consolidation therapy was more toxic than IcE, however, the treatment-related death rate was not significantly different. There was no difference between the 2 consolidation arms for relapse-free survival at 3 years (49% for ICE vs 46% for IcE; P = .66), survival following randomization (61% vs 62%; P = .91), or the cumulative incidence of relapse (43% vs 51%; P = .31), and there was no difference within cytogenetic risk groups. Intensive induction chemotherapy incorporating high-dose cytarabine results in high complete remission rates, but further intensive consolidation treatment does not appear to confer additional benefit.

SURVEY ON THE LENGTH OF STAY FOR THE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: AN APPLICATION ON ATATURK CHEST DISEASE HOSPITAL

SUMMARY This study has been made on the patients with Chronic Obstructive Pulmonary Disease (COPD) in Ataturk Chest Disease Hospital in order to put forth the factors pro- longing the length of stay, decreasing the discharge time, preventing the nonessential staying and contributing to servicing more patients with the existing available condi- tions of the hospital. During the research, the files, serv- ice protocol books and outlet summaries of 113 patients staying in Non Tuberculosis (TB) clinics between 1-31 January 2001 were examined. It was researched that how the variables such as age, staying service, sex, domicile, staying status, educational level, number of COPD diag- nosis had before, additional diseases, COPD age, com- plication and reasons for complication, effected the length of stay. According to the results of the research, there are meaningful relations between the average length of stay and educational level, number of COPD diagnosis, additional diseases, COPD age, existence of complication and reasons for complication. On the other hand, staying service, age of the patient, sex, domicile, staying status are not related meaningfully with the aver- age length of stay statistically.

Prognostic factors influencing feasibility of cytogenetic and molecular analysis in leukapheresis products in chronic myelogenous leukemia patients.

Conventional cytogenetic (CC) study and molecular analysis were performed in 150 leukapheresis products from 36 patients diagnosed with chronic myelogenous leukemia who were included in an autologous stem cell transplantation program. The aims of the study were to evaluate the effectiveness of these two methods for the detection of residual disease in the harvest and to identify the factors influencing the number of cycling cells present in the apheresis products. Progenitor cell mobilization procedures performed late after diagnosis (>12 months), a short interval between interferon-alpha discontinuation and mobilization (<3.5 months), and an intensive mobilization regimen (idarubicin, cytarabine, and etoposide, ICE protocol) were associated with a low probability of obtaining 25 metaphases, which was achieved in only 41 instances (25% of the samples). In 38 samples, less than ten metaphases were obtained; a peripheral blood leukocyte count <1.0x10(9)/l at mobilization and mononuclear cell counts in the bag <0.5x10(8)/kg significantly increased the probability to obtain less than ten metaphases for CC analysis. Previous interferon-alpha treatment during > or =12 months and low mononuclear cell counts in the bag (<0.5x10(8)/kg) increased the probability of not obtaining mitosis for cytogenetic analysis. Molecular analysis by the polymerase chain reaction (PCR) technique did not give discriminate information in the samples not evaluable by cytogenetics due to the high frequency of PCR-positive results. We conclude that new techniques such as hypermetaphase fluorescence in situ hybridization (FISH), interphase FISH, or quantitative PCR need to be routinely employed in the study of leukapheresis samples of chronic myelogenous leukemia patients for a better assessment of the neoplastic contamination of the infused products.

Mini-Ice Protocol is Better Than High-Dose Hydroxyurea to Mobilize Ph-Negative Cells in Earlier Phases of Chronic Myelogenous Leukemia

We refer to the recent paper by Johnson et al.[1] regarding the use of high-dose hydroxyurea to mobilize Ph-negative progenitor cells. We have already dealt with this topic in the report of our results with ICE and mini- ICE[2]. In that occasion, we showed that these protocols were able to determine the mobilization of Ph-negative cells even in patients cytoge-netically refractory to IFN-α and/or in advanced phases of disease. These results were recently confirmed by an international study[3]. Generally speaking, these protocols gave better results when employed in earlier phases of disease; moreover, mini-ICE protocol proved to be extremely well tolerated, administered in many patients on an outpatient basis and of capable obtaining the same cytogenetic results as the ICE protocol[4]. From the update reported by Johnson et al., no improvement occurs with respect to the previous one published in 1996[5] mainly in respect to the complete failure of this protocol to harvest complete or partial Ph-negative c...

ICE protocol as conditioning regimen in autologous bone marrow transplantation in high-grade non-Hodgkin's lymphoma

ICE protocol as conditioning regimen in autologous bone marrow transplantation in high-grade non-Hodgkin's lymphoma

Effective mobilization of Philadelphia-chromosome-negative cells in chronic myelogenous leukaemia patients using a less intensive regimen.

To determine if reducing the intensity of the mobilizing chemotherapy protocol used would alter the number and/or quality of the progenitors mobilized in patients with chronic myelogenous leukaemia (CML), we undertook a pilot study. 36 consecutive CML patients previously treated only with hydroxyurea were given mobilization therapy within 12 months of diagnosis. 17 patients were treated by the ICE protocol and 19 patients received the mini-ICE protocol. The leukapheresis product collected from 22/36 patients (62%) was entirely Ph-negative. The cytogenetic results between ICE and mini-ICE-treated protocols were not significant, although the reduction in median days of hospitalization required for the mini-ICE versus the ICE protocol was highly significant (P < 0.0001). There was no significant difference in the yield of CD34+ cells and CFU-GM collected. No patient in the mini-ICE protocol experienced high-grade oral mucositis and GI toxicity whereas three such cases occurred with the ICE protocol. No patient died of the mobilization procedure in either group.

Expression and functional activity of P-glycoprotein in adult acute myelogenous leukemia patients.

Expression and functional activity of P-glycoprotein (P-gp) were measured in 182 acute myelogenous leukemia (AML) patients: 136 patients were treated with the AML-6 protocol (EORTC), containing daunorubicin, vincristine, and conventional-dose cytarabine (ara-C), and 21 patients received idarubicin, vepeside, and conventional-dose ara-C (ICE-AML-10 protocol/EORTC). An additional 25 patients were treated with a dose of idarubicin and ara-C, modified as compared with the ICE protocol, but with the same dose of etopside (ICE-I protocol). P-gp was determined using monoclonal antibody 4E3.16 and functional activity using the rhodamine 123 accumulation test. P-gp positivity was defined as a Kolmogorov Smirnov (KS) D value > or = 0.15, P-gp negativity as a KS D value < 0.15. P-gp activity was defined as a ratio of mean rhodamine 123 accumulation with/without verapamil. In AML patients at primary diagnosis and early relapse/refractoriness a significant (p < 0.05) difference between P-gp-positive and P-gp-negative patients was ascertained using the AML-6 protocol; the difference corresponded to the complete remission rate. For ICE- and ICE-I-treated AML patients at primary diagnosis this significance was not shown. Compared with AML patients at primary diagnosis and patients at early relapse or refractoriness, a significantly (p < 0.05) increased incidence of non-pumping P-gp and a trend (p = 0.054) to a higher percentage of non-P-gp-related mechanisms in AML patients at late relapse was determined. When the AML-6 protocol is used, age, activated P-gp, and CD34 expression are independent prognostic factors in AML patients. A test system which determines a functional P-gp overexpression is a major tool for identifying a group of AML patients with a poor prognosis. In order to effectively use so-called P-gp modulator substances, the degree of P-gp expression, the activated or nonactivated P-gp condition, and detection of non-P-gp-related resistance mechanisms are of utmost interest for optimal design and analysis of P-gp modulator trials and for understanding the complexity of chemotherapy-related resistance mechanisms in patients.