Prognostic factors in adolescent and adult patients with acute lymphoblastic leukemia with two protocols of chemotherapy: a cross-sectional study.

BACKGROUND: We evaluated the clinical, laboratory, and prognostic factors in adolescent and adult patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: In this observational, retrospective, cross-sectional study, we examined the medical records of all consecutive patients with ALL admitted to a public hospital in Brazil from 1990 to 2005. RESULTS: Of the 102 patients included, 88 were treated with 2 protocols of chemotherapy (Berlin-Frankfurt-Münster [BFM] 86 modified [BFM-86M] and UCLA [University of California, Los Angeles] protocol). The complete remission (CR), disease-free survival, and overall survival (OS) rate was 70.6%, 27%, and 30.5%, respectively (median follow-up, 49 months). Age < 18 years and no leukemic infiltration in the central nervous system (CNS) at diagnosis were positively associated with CR (P = .03); no bleeding and hepatomegaly at diagnosis and age < 35 years were associated with better OS on multivariate analyses of the whole population (P = .01). OS at 4 years was superior with BFM-86M than with UCLA (49.5% vs. 16%; P = .004), especially in young adults without risk factors. CONCLUSION: We identified age as the most important prognostic factor in patients with ALL. CNS infiltration, hepatomegaly, and bleeding were associated with lower OS but must be validated in future research with South American populations and worldwide. The BFM-86M protocol can be considered a therapeutic option for young adults (age < 35 years) without adverse prognostic factors. For other patients with ALL, we emphasize the need for different therapeutic approaches.

Detection of Plasmodium falciparum and Plasmodium vivax subclinical infection in non-endemic region: implications for blood transfusion and malaria epidemiology.

BACKGROUND: In Brazil, malaria is endemic in the Amazon River basin and non-endemic in the extra-Amazon region, which includes areas of São Paulo state. In this state, a number of autochthonous cases of malaria occur annually, and the prevalence of subclinical infection is unknown. Asymptomatic infections may remain undetected, maintaining transmission of the pathogen, including by blood transfusion. In these report it has been described subclinical Plasmodium infection in blood donors from a blood transfusion centre in São Paulo, Brazil. METHODS: In this cross-sectional study, representative samples of blood were obtained from 1,108 healthy blood donors at the Fundação Pró-Sangue Hemocentro de São Paulo, the main blood transfusion centre in São Paulo. Malaria exposure was defined by the home region (exposed: forest region; non-exposed: non-forest region). Real-time PCR was used to detect Plasmodium falciparum and Plasmodium vivax. Subclinical malaria cases were geo-referenced. RESULTS: Eighty-four (7.41%) blood donors tested positive for Plasmodium; 57 of these were infected by P. falciparum, 25 by P. vivax, and 2 by both. The prevalence of P. falciparum and P. vivax was 5.14 and 2.26, respectively. The overall prevalence ratio (PR) was 3.23 (95% confidence interval (CI) 2.03, 5.13); P. falciparum PR was 16.11 (95% CI 5.87, 44.21) and P. vivax PR was 0.47 (95% CI 0.2, 1.12). Plasmodium falciparum subclinical malaria infection in the Atlantic Forest domain was present in the mountain regions while P. vivax infection was observed in cities from forest-surrounded areas. CONCLUSIONS: The presence of Plasmodium in healthy blood donors from a region known as non-endemic, which is important in the context of transfusion biosafety, was described. Infected recipients may become asymptomatic carriers and a reservoir for parasites, maintaining their transmission. Furthermore, P. falciparum PR was positively associated with the forest environment, and P. vivax was associated with forest fragmentation.

Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib.

Patients in complete cytogenetic response (CCyR) with detectable BCR-ABL1 after ≥2 years on imatinib were randomized to nilotinib (400 mg twice daily, n = 104) or continued imatinib (n = 103) in the Evaluating Nilotinib Efficacy and Safety in clinical Trials-Complete Molecular Response (ENESTcmr) trial. By 1 and 2 years, confirmed undetectable BCR-ABL1 was achieved by 12.5% vs 5.8% (P = .108) and 22.1% vs 8.7% of patients in the nilotinib and imatinib arms, respectively (P = .0087). Among patients without molecular response 4.5 (BCR-ABL1(IS) ≤0.0032%; MR(4.5)) and those without major molecular response at study start, MR(4.5) by 2 years was achieved by 42.9% vs 20.8% and 29.2% vs 3.6% of patients in the nilotinib and imatinib arms, respectively. No patient in the nilotinib arm lost CCyR, vs 3 in the imatinib arm. Adverse events were more common in the nilotinib arm, as expected with the introduction of a new drug vs remaining on a well-tolerated drug. The safety profile of nilotinib was consistent with other reported studies. In summary, switching to nilotinib enabled more patients with chronic myeloid leukemia in chronic phase (CML-CP) to sustain lower levels of disease burden vs remaining on imatinib. This trial was registered at www.clinicaltrials.gov as #NCT00760877.

Evaluation of long-term outcomes, cytogenetic and molecular responses with imatinib mesylate in early and late chronic-phase chronic myeloid leukemia: a report from a single institute.

Here we compare the management and survival outcomes of chronic myeloid leukemia (CML) patients who had early or late imatinib mesylate (IM) therapy. The cytogenetic and molecular responses of 189 CML patients were analyzed. Of this group, 121 patients were classified as the early chronic phase (ECP) group and started IM within 12 months of diagnosis. The other 68 patients were classified as the late chronic phase (LCP) group who had been treated with interferon (IFN)-alpha-2 and crossed over to IM more than 12 months after diagnosis. The overall rates of complete cytogenetic response (CCyR) and major molecular response (MMR) at last follow-up were 83.6 and 78.1% in the ECP and LCP groups, respectively. The CCyR rates were 89.3 (for ECP patients) versus 73.5% (for LCP patients; p < 0.0001). At last follow-up, 82.4% ECP and 64.2% LCP patients had achieved an MMR (p < 0.0001). No significant differences were noted between the two groups with regard to survival outcomes. Our experience reveals that IM is an effective rescue therapy in most CML LCP patients who are intolerant or in whom IFN-alpha therapy fails. Such therapeutic options should be considered in LCP patients, particularly in countries where IM may not be available.

Dasatinib overrides imatinib resistance mediated by the F359I residue mutation in two patients with chronic myeloid leukemia.

Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones.

Expanding Nilotinib Access in Clinical Trials (ENACT), an open-label multicenter study of oral nilotinib in adult patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase or blast crisis.

Nilotinib has shown favorable safety in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic (CML-CP) or accelerated phase (CML-AP) who failed prior imatinib, and superior efficacy over imatinib in newly diagnosed Ph+ patients with CML-CP. Reported here are the efficacy and safety data for patients in CML-AP (n = 181) or blast crisis (CML-BC) (n = 190; myeloid BC, 133; lymphoid BC, 50; unknown, seven) enrolled in an expanded access phase IIIb study. Non-hematologic adverse events were mostly mild to moderate. Drug-related myelosuppression was generally manageable with dose reductions or interruptions and infrequently led to discontinuation of nilotinib. Drug-related grade 3/4 elevations in serum bilirubin and lipase were infrequent. While an analysis of efficacy was not the primary objective of this study, significant hematologic and cytogenetic responses were observed. These results support the safety and efficacy of nilotinib in patients with advanced CML in AP and BC.

Outpatient treatment with intravenous antimicrobial therapy and oral levofloxacin in patients with febrile neutropenia and hematological malignancies.

The purpose of this study was to evaluate outcomes such as success of the initial therapy, failure of outpatient treatment, and death in outpatient treatment during intravenous antimicrobial therapy in patients with febrile neutropenia (FN) and hematological malignancies. In addition, clinical and laboratory data and the Multinational Association for Supportive Care of Cancer index (MASCC) were compared with failure of outpatient treatment and death. In a retrospective study, we evaluated FN following chemotherapy events that were treated initially with cefepime, with or without teicoplanin and replaced by levofloxacin after 48 h of defervescence in patients with good general conditions and ANC>500/mm3. Of the 178 FN episodes occurred in 126 patients, we observed success of the initial therapy in 63.5% of the events, failure of outpatient treatment in 20.8%, and death in 6.2%. The success rate of oral levofloxacin after defervescence was 99% (95 out of 96). Using multivariate analysis, significant risks of failure of outpatient treatment were found to be smoking (odds ratio (OR) 3.14, confidence interval (CI) 1.14-8.66; p=0.027) and serum creatinine levels>1.2 mg/dL (OR 7.97, CI 2.19-28.95; p=0.002). With regard to death, the risk found was oxygen saturation by pulse oximetry<95% (OR 5.8, IC 1.50-22.56; p=0.011). Using the MASCC index, 165 events were classified as low risk and 13 as high risk. Failure of outpatient treatment was reported in seven (53.8%) high-risk and 30 (18.2%) low-risk episodes (p=0.006). In addition, death occurred in seven (4.2%) low-risk and four (30.8%) high-risk events (p=0.004). Ours results show that MASCC index was able to identify patients with high risk. In addition, non-smoking, serum creatinine levels≤1.2 mg/dL, and oxygen saturation by pulse oximetry≥95% were protection factors.

Response to dasatinib in a patient with concomitant chronic myeloid leukemia and chronic lymphocytic leukemia.

While chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are common diseases in the elderly, they rarely occur simultaneously in the same patient. Here we present the case of a 77-year-old patient diagnosed with CML in the chronic phase who showed an optimal response to 400 mg/day of imatinib. This patient progressed to Binet B-CLL with an 11q22.3 deletion and CD38 positivity in the 4th month of treatment. During the follow-up, his lymphocyte number doubled in <6 months. Based on previous reports, dasatinib was chosen instead of imatinib. After 6 months of treatment with 100 mg/day of dasatinib, the patient demonstrated a partial response, characterized by the regression of lymph node enlargement, a hemoglobin level of 10.7 g/dl, neutrophils of 1.7 × 10(9)/l, a 82% reduction in the lymphocyte number and an increase in cytotoxic CD8+ and large granular lymphocytes. This partial response has persisted to the present time. While little data have been published regarding the in vitro effect of dasatinib monotherapy for CLL, this case report provides some evidence of the clinical activity of dasatinib in CLL.

Efficacy and tolerability after unusually low doses of dasatinib in chronic myeloid leukemia patients intolerant to standard-dose dasatinib therapy.

We report our experience in 4 patients with chronic myeloid leukemia (CML) who had discontinued imatinib as a result of adverse events and had switched to dasatinib. The chronic phase (n 2) and accelerated phase (n 2) CML patients received dasatinib at starting dose of 100 and 140 mg once daily, respectively. Reappearance of hematological toxicity was observed in 3 patients and pancreatitis in one patient. Treatment was given at a lower dose and patients were followed. The median follow-up was 13 months and the median dose of dasatinib until achievement of complete cytogenetic remission (CCyR) was 60 mg daily (range = 20 to 120 mg). All four patients had achieved CCyR at a median of 4 months (range = 3 to 5 months) and among them, three had also achieved major molecular remission. We conclude that low-dose dasatinib therapy in intolerant patients appears safe and efficacious and may be tried before drug discontinuation.

Early Detection of t(8;21) Chromosomal Translocations During Treatment of PML-RARA Positive Acute Promyelocytic Leukemia: A Case Study.

Here we describe a female patient who developed acute promyelocytic leukemia (APL) characterized by t(l5;17) translocation at diagnosis. The patient began treatment with all-trans retinoic acid (ATRA) + chemotherapy. During follow up, the patient was found to be negative for the t(15;17) transcript after 3 months of therapy which remained undetectable, thereafter. However, the emergence of a small clone with a t(8;21) abnormality was observed in the bone marrow and peripheral blood (PB) cells between 3 and 18 months following treatment initiation. The abnormal translocation observed in PB cells obtained at 3 months was detected after the second cycle of consolidation therapy and reappeared at 15 months during maintenance treatment, a period without ATRA. Although based on a single case, we conclude that genetic screening of multiple translocations in AML patients should be requested to allow early identification of other emerging clones during therapy that may manifest clinically following treatment.

Impact of allogeneic 2-RBC apheresis on iron stores of Brazilian blood donors.

One limiting factor for automated two-red blood cells collections (2-RBC) is its potential iron depletion. We analyzed hematological parameters and iron balance before, two and four months after 2-RBC of 96 non-supplemented male donors. Four months after 2-RBC, ferritin level was significantly lower (P<0.01) than baseline levels and the number of donors who presented ferritin <30 ng/ml increased from 18 to 47. We concluded that four months was not sufficient for iron recuperation in the population studied. In an attempt to avoid iron depletion after 2-RBC, we recommend augmentation in the interval between blood donations and pre-donation ferritin measurement.

Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up.

Dasatinib is the most potent BCR-ABL inhibitor, with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Studies have demonstrated the benefits of dasatinib 70 mg twice daily in patients with accelerated-phase chronic myeloid leukemia intolerant or resistant to imatinib. A phase 3 study compared the efficacy and safety of dasatinib 140 mg once daily with the current twice-daily regimen. Here, results from the subgroup with accelerated-phase chronic myeloid leukemia (n = 317) with a median follow-up of 15 months (treatment duration, 0.03-31.15 months) are reported. Among patients randomized to once-daily (n = 158) or twice-daily (n = 159) treatment, rates of major hematologic and cytogenetic responses were comparable (major hematologic response, 66% vs 68%; major cytogenetic response, 39% vs 43%, respectively). Estimated progression-free survival rates at 24 months were 51% and 55%, whereas overall survival rates were 63% versus 72%. Once-daily treatment was associated with an improved safety profile. In particular, significantly fewer patients in the once-daily group experienced a pleural effusion (all grades, 20% vs 39% P < .001). These results demonstrate that dasatinib 140 mg once daily has similar efficacy to dasatinib 70 mg twice daily but with an improved safety profile. This trial is registered at www.clinicaltrials.gov as #CA180-035.

Anemia screening in potential female blood donors: comparison of two different quantitative methods.

BACKGROUND: Anemia screening before blood donation requires an accurate, quick, practical, and easy method with minimal discomfort for the donors. The aim of this study was to compare the accuracy of two quantitative methods of anemia screening: the HemoCue 201(+) (Aktiebolaget Leo Diagnostics) hemoglobin (Hb) and microhematocrit (micro-Hct) tests. STUDY DESIGN AND METHODS: Two blood samples of a single fingerstick were obtained from 969 unselected potential female donors to determine the Hb by HemoCue 201(+) and micro-Hct using HemataSTAT II (Separation Technology, Inc.), in alternating order. From each participant, a venous blood sample was drawn and run in an automatic hematology analyzer (ABX Pentra 60, ABX Diagnostics). Considering results of ABX Pentra 60 as true values, the sensitivity and specificity of HemoCue 201(+) and micro-Hct as screening methods were compared, using a venous Hb level of 12.0 g per dL as cutoff for anemia. RESULTS: The sensitivities of the HemoCue 201(+) and HemataSTAT II in detecting anemia were 56 percent (95% confidence interval [CI], 46.1%-65.5%) and 39.5 percent (95% CI, 30.2%-49.3%), respectively (p < 0.001). Analyzing only candidates with a venous Hb level lower than 11.0 g per dL, the deferral rate was 100 percent by HemoCue 201(+) and 77 percent by HemataSTAT II. The specificities of the methods were 93.5 and 93.2 percent, respectively. CONCLUSION: The HemoCue 201(+) showed greater discriminating power for detecting anemia in prospective blood donors than the micro-Hct method. Both presented equivalent deferral error rates of nonanemic potential donors. Compared to the micro-Hct, HemoCue 201(+) reduces the risk of anemic female donors giving blood, specially for those with lower Hb levels, without increasing the deferral of nonanemic potential donors.

The use of imatinib mesylate as a lifesaving treatment of chronic myeloid leukemia relapse after bone marrow transplantation.

We describe the response of imatinib as lifesaving treatment of chronic myeloid leukemia (CML) relapse in seven patients who underwent allogeneic bone marrow transplantation (alloBMT) at our institution over a period of 4 years. Retrospective analysis of their medical records revealed that a mean age at transplant was 45.2 years. The median time to diagnosis was 7.4 years after transplant. At relapse, four, two, and one patients were classified as having hematologic, major molecular, and cytogenetic relapse, respectively. At imatinib initiation, five had CML in a chronic phase, while one patient was diagnosed as having accelerated phase and blast crisis. All these patients could be evaluated for the therapeutic efficacy. At a mean of follow-up of 1.9 years of therapy, all evaluable patients achieved major molecular response without compromising safety. Consistent with available data, our results indicate that imatinib is safe and effective treatment option for patients with relapse after BMT.

Dez anos de experiência em controle de qualidade em imuno-hematologia / Ten years of experience of quality control in immunohematology

A medicina transfusional tem como objetivo garantir a qualidade e quantidade do sangue, componentes e serviços oferecidos à comunidade, e, dentro desse contexto, a análise dos reagentes imuno-hematológicos é crítica para a realização dos testes pré-transfusionais e, consequentemente, uma transfusão segura. É responsabilidade do controle de qualidade o constante aperfeiçoamento de testes que analisam a qualidade dos reagentes e equipamentos utilizados. Esse trabalho tem por objetivo apresentar os resultados alcançados em dez anos de experiência do Departamento de Controle de Qualidade em Imuno-hematologia da Fundação Pró-Sangue / Hemocentro de São Paulo. No período de janeiro de 1997 a dezembro de 2007 foram realizadas análises em 3.417 reagentes imuno-hematológicos por ocasião da aquisição do reagente e por solicitação de reavaliação (durante o uso). As análises incluíram desde a inspeção visual no recebimento a testes laboratoriais específicos para cada tipo de reagente. Dos 3.417 lotes analisados (média=310/ano, mediana=252/ano), 94 (2,7 por cento) foram reprovados (média=8,54/ano, mediana=7,00 ± 7,79/ano). Uma vez aprovado pelo controle de qualidade à aquisição, nenhum reagente imunohematológico foi reprovado durante o uso desde 2004. Podemos concluir que, para implementação de um sistema de controle de qualidade de reagentes imuno-hematológicos, não é necessário uso de reagentes ou equipamentos altamente especializados, pois os mesmos são utilizados na rotina laboratorial, como também não envolvem alta complexidade na execução das análises. Podemos enfim considerar que a implementação do controle de qualidade em Imuno-hematologia contribui para o aumento da segurança transfusional e é factível de realização nos mais diferentes níveis de complexidade dos serviços hemoterápicos.

Transfusion medicine has the purpose of guaranteeing the quality and quantity of blood, blood derivatives and services offered to the community. Thus, the analysis of serological reagents is critical in pre-transfusion testing and, consequently, reliable transfusions. A constant improvement in the tests that analyze the quality of reagents and equipment utilized is the responsibility of quality control. This paper aims at presenting the results and experience achieved over 10 years in the Department of Quality Control in Immunohematology at Fundação Pró-Sangue / Hemocentro de São Paulo. In the period of January 1997 to December 2007 we carried out analyses of 3,417 serological reagents at acquisition and/or during their use. The analyses included from visual inspection to specific laboratory tests for each kind of reagent. Of the 3,417 lots analyzed (mean = 310/year, median = 252/year), 94 (2.7 percent - median=8.54/year) failed the tests. From 2004 to date, once the reagents were approved, none failed during use. The implementation of a quality control system with standardized techniques is important for the adequate utilization of serological reagents. This system accomplished by retroactive control of the reagents, contributed to the safety and reliability of results in immunohematology testing.

Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia.

PURPOSE: Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose- and schedule-optimization study is reported. PATIENTS AND METHODS: In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1:1:1:1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. RESULTS: With minimum follow-up of 6 months (median treatment duration, 8 months; range, < 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). CONCLUSION: Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.

Detecção de Aspergillus sp pela técnica de PCR-nested em pacientes submetidos a transplante de medula óssea: [carta ao editor] / Detection of Aspergillus sp in bone marrow transplant patients by PCR-nested technique: [letter to editor]

Invasive aspergillosis is an important cause of mortality in long-term neutropenic patients, particularly after bone marrow (B.M.T.) and solid organ transplantation. More than 90% of invasive fungal infections in immunocompromised patients can be attributed to Candida and Aspergillus. To date, there is no fast, reliable and feasible test for Aspergillus infection detection in routine procedures. In the present report, a nested PCR technique, developed to detect Aspergillus infection, is described. In our study, the sensitivity, specificity, positive and negative values using this approach were 100%, 94.4%, 83.3%, and 100%, respectively.

Modified Magrath IVAC regimen as second-line therapy for relapsed or refractory aggressive non-Hodgkin's lymphoma in developing countries: the experience of a single center in Brazil.

BACKGROUND: The purpose of this retrospective study was to investigate the efficacy, toxicity and mobilization rate after modified Magrath IVAC (mIVAC) chemotherapy regimen prescribed in relapsed disease (RD) or primary refractory disease (PRD) in aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Twenty-four patients (16 males, 8 females) aged 18-59 years (median age 37 year) were analyzed. The most frequent histopathological subgroup was diffuse large B-cell lymphoma (DLCL-B) (n=21/24), 13 (54%) were considered RD and 11 (46%) PRD. The mIVAC consisted of ifosfamide (IFM), high dose cytarabine and etoposide repeated every 28 days. RESULTS: The overall response (OR) after three cycles of mIVAC was 66. 6%. Among the patients with PRD, OR was 45.5% (5 out of 11) and with RD was 86.4%, p>0.05, however, it was observed in RD better complete response (CR) than PRD 53.8x9.1% (p<0.05). Eighty-eight percent (14 out of 16) of patients with chemosensitive disease to mIVAC underwent autologous stem cell transplantation (ASCT). The median number of collected CD34+ cells was 2.86x10(6) (range 2.17x10(6) to 4.9x10(6)). The median overall survival rate (OS) for chemosensitive to mIVAC was 16.3 months, with a median follow-up of 16 months. Grades III-IV neutropenia was observed in 85.6% per cycles and grades III-IV thrombocytopenia in 87.5%. Grades III-IV febrile neutropenia was the most common nonhematological toxicity, it occurred in 28% of the cycles and no deaths by toxicity were observed. DISCUSSION: Although a statistic comparative study was not carried out for these 24 patients, the rate of OR to mIVAC was alike the other second-line infusion regimens. The mobilization failure rate was 57.1% and it was similar to other regimens with high dose cytarabine, but it did not limit performed ASCT.