Acute Myeloid Leukemia in Mexico: The Specific Challenges of a Developing Country. Results From a Multicenter National Registry.

BACKGROUND: In the past decades, long-term survival outcomes for younger patients with acute myeloid leukemia (AML) have improved. Nonetheless, developing nations might be lagging behind, highlighting the need to assess real-world outcomes in such regions. METHODS: We performed a multicenter retrospective study, which included patients with AML diagnosed between January 2013 and December 2017 from 13 centers in Mexico. RESULTS: A total of 525 patients with AML met the inclusion criteria and were included in the study. Median age for the entire cohort was 47 years. The patients were classified according to cytogenetic risk: favorable 16.0%, intermediate 55.6%, and unfavorable 28.4%. Most patients received intensive chemotherapy (80.2%), and among these 74.1% underwent a 7 + 3 induction regimen. A complete remission was achieved in 71.3% of patients. Induction-related mortality occurred in 17.8% and we identify the following as independent risk factors: >60 years (odds ratio [OR] 2.09 [1.09-4.02]), Eastern Cooperative Oncology Group >2 (OR 4.82 [2.46-9.43]), prior solid tumor (OR 3.8 [1.24-11.59]) and active infection (OR 1.82 [1.06-3.12]). Further, allogeneic hematopoietic stem-cell transplantation (AlloHSCT) was performed in 8.2% in CR1. The 3-year overall survival (OS) was 34.8%. In a multivariate analysis, several factors were independently associated with a worse OS, including secondary AML (hazard ratio [HR] 2.14 [1.15-4.01]) and unfavorable cytogenetic risk (HR 1.81 [1.16-2.82]), whereas maintenance therapy (HR 0.53 [0.32-0.86]) and AlloHSCT (HR 0.40 [0.17-0.94]) were associated with better OS. CONCLUSIONS: This is the first multicenter report analyzing AML survival in Mexico. Challenges in this setting include a high induction-related mortality and low AlloHSCT rate, which should be addressed to improve outcomes.

Survival analysis of adult patients with ALL in Mexico City: first report from the Acute Leukemia Workgroup (ALWG) (GTLA).

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009-2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia-positive was present in 16.7%. The most commonly used treatment regimen was hyper-CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3-year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained.

Survival and treatment response in adults with acute promyelocytic leukemia treated with a modified International Consortium on Acute Promyelocytic Leukemia protocol

ABSTRACT Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.

Survival and treatment response in adults with acute promyelocytic leukemia treated with a modified International Consortium on Acute Promyelocytic Leukemia protocol.

Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.

Outcomes of Substituting Oral Fludarabine for Intravenous Fludarabine in Combination with Cytarabine and Filgrastim for Treatment of Primary Refractory or Relapsed Acute Leukemias.

BACKGROUND: Treatment of relapsed/refractory acute myeloid or lymphoid leukemia consists of salvage chemotherapy followed by allogeneic hematopoietic stem-cell transplantation. Intravenous fludarabine, cytarabine, and filgrastim is an effective regimen in this setting. In view of the lack of availability of intravenous fludarabine in Mexico from 2009-2013, we substituted an equivalent oral fludarabine dose (40 mg) for the intravenous formulation. OBJECTIVE: This is a retrospective comparison of the toxicity and effectiveness of oral fludarabine, cytarabine, and filgrastim versus intravenous fludarabine, cytarabine and filgrastim. RESULTS: A total of 44 patients with relapsed/refractory acute myeloid leukemia or acute lymphoid leukemia treated in an academic medical center from 2005-2013 with oral fludarabine, cytarabine and filgrastim (21 patients) or intravenous fludarabine, cytarabine and filgrastim (23 patients) were included in the analysis. There was a trend towards a higher complete remission rate and a longer overall survival following intravenous fludarabine, cytarabine, and filgrastim as compared with oral fludarabine, cytarabine, and filgrastim: complete remission rates 39.1 vs. 23.8% (p = 0.342) and overall survival 6.14 vs. 10.78 months (p = 0.363), respectively. A higher incidence of neutropenic fever (100 vs. 76.2%; p = 0.019) and septic shock (34.8 vs. 0%; p = 0.003) and a longer hospitalization (26.8 vs. 19.4 days; p = 0.046) were observed with intravenous fludarabine, cytarabine, and filgrastim. In multivariate analysis, factors associated with a shorter survival were septic shock (HR: 3.93; 95% CI: 1.67-9.25; p = 0.002) and a higher number of previous treatments (HR: 2.5; 95% CI: 1.26-4.99; p = 0.009). Complete remission was associated with better survival (HR: 0.18; 95% CI: 0.08-0.44; p < 0.001). CONCLUSIONS: Further studies are needed to determine the optimal dose and timing of oral fludarabine when given as part of the fludarabine, cytarabine, and filgrastim regimen for relapsed/refractory acute leukemia. Our data suggest that the dose of oral fludarabine used, 40 mg/m² per day for five days, may be a lower bioequivalent dose to the intravenous dose in fludarabine, cytarabine, and filgrastim.

Thalidomide and Dexamethasone Induction Therapy Until Best Response in Recently Diagnosed Patients with Multiple Myeloma: Results From a Pilot Study.

BACKGROUND: Novel therapies for multiple myeloma are not affordable for all healthcare systems. OBJECTIVES: The objectives of this study were to evaluate the response rates, overall survival, event-free survival, and toxicity of thalidomide and dexamethasone administered until best response in recently diagnosed patients with multiple myeloma. METHODS: All recently diagnosed multiple myeloma patients meeting the inclusion criteria received the same treatment with thalidomide and dexamethasone. RESULTS: We studied 28 patients. Overall response rate was 75%. Complete response, partial response, and very good partial response were 25.0, 32.1, and 17.9%, respectively. The most frequent adverse event related to therapy was neuropathy. Median overall survival was 66 months, and median event-free survival was 39 months (range, 27.6-50.4). Variables that negatively affected overall survival on multivariate analysis included the presence of extramedullary disease, t(14;16), and chromosome 13 deletion. CONCLUSIONS: Induction therapy with thalidomide and dexamethasone until obtaining the best response in patients with recently diagnosed multiple myeloma was a useful and safe strategy. It represents an alternative for patients with limited access to costly drugs.

Prognostic Factors, Response to Treatment, and Survival in Patients With Chronic Myeloid Leukemia in Blast Phase: A Single-Institution Survey.

INTRODUCTION: Data from 51 patients (23 women) with chronic myeloid leukemia (CML) in blast phase (BP) were analyzed in order to identify prognostic factors for complete hematologic response (CHR) and survival. PATIENTS AND METHODS: Forty-four patients experienced disease progression from chronic or accelerated phase, and 7 cases presented as CML-BP. Thirteen patients (25.5%) had extramedullary involvement at diagnosis, and 71% were myeloid BP. Clonal evolution was identified in 53% of the cases, and the abnormalities most frequently observed were isochromosome (17q), double Philadelphia chromosome, and trisomy 8. Forty-five patients received treatment: 60% chemotherapy (CT) alone and 40% CT plus tyrosine kinase inhibitors (TKI) or TKI alone; 42% of them experienced CHR. RESULTS: Median overall survival (OS) in patients whose disease responded to treatment was 7 months (95% confidence interval, 1.7-6.2 months), with a median disease-free survival of 5 months (95% confidence interval, 2.8-5.8 months). One out of 3 patients who underwent hematopoietic stem-cell transplantation remains alive. Multivariate analysis revealed that lymphoid BP and TKI therapy had a statistically significant positive impact as prognostic factors for CHR. In the multivariate analysis, age > 60 years, hemoglobin < 10 g/dL, and complex karyotype were statistically significant negative prognostic factors for OS. There was no statistical significant difference in OS between patients who received only CT (1988-2002) with those treated with CT plus TKI (2003-2013). CONCLUSION: This is the first study in Mexico to report prognostic factors associated with CHR and OS in patients with CML-BP.

Small MAF genes variants and chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is one of the most frequent hematological neoplasia worldwide. The abnormal accumulation of reactive oxygen species may be an important factor in CML development. The transcription factor NRF2 can regulate the transcription of a battery of antioxidant and detoxificant genes after heterodimerizing with small-Maf proteins. Although the participation of NRF2 in the development of chronic degenerative diseases has been thoroughly studied, the role of small-Maf genes has not been documented. We have identified polymorphisms in the three MAF genes (F, G and K) and assessed their association with CML. Over 266 subjects with CML and 399 unrelated healthy donors have been studied. After sequencing each MAF gene by Sanger technology, we found 17 variants in MAFF gene, eight in MAFG and seven in MAFK. In the case-control study, the homozygote genotype CC for the rs9610915 SNP of MAFF was significantly associated with CML. The frequency of the ACC haplotype from MAFK was significantly lower than controls. After stratification by gender, the ACC and GTG haplotypes were associated only with males with CML. These novel data suggest an association between MAFF and MAFG and the development of CML.

Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in México.

Mixed phenotype acute leukemia (MPAL) in adults represents nearly 2 to 5 % of all acute leukemia cases. There are two large studies throughout the world and only case reports and small series have been reported in Latin America. This study retrospectively analyses the clinical characteristics and survival of 27 patients with MPAL evaluated in three medical institutions of Mexico. All cases meet World Health Organization 2008 criteria; 70.3 % of patients had B lymphoid/myeloid lineage MPAL. Induction chemotherapy protocols included 7 + 3 hyper-CVAD, high-density schedules, and pediatric-like regimens such as New York II and total XI. Complete remission was achieved in 23/27 patients (85.2 %). Only one patient died due to chemotherapy-induced aplasia during remission induction (5.2 %). In 68 % of cases, we were able to administer maintenance therapy as a regimen in lymphoblastic leukemia. At the time of analysis, 70.4 % of the patients in the entire cohort had died mainly as result of disease progression (73.6 %). Disease-free survival was 13 months (95 % CI, 9.6-16.3 months) and overall survival was 14.8 months (95 % CI 13.4-16.27). Survival rates are low and standardized therapy for the management of this type of leukemia is still lacking. This is the largest series reported in Mexico and to the best of our knowledge in Latin America.

Incidence of thrombosis in adults with acute leukemia: a single center experience in Mexico.

BACKGROUND: Acute leukemias are hematopoietic malignancies that may be accompanied by hemostatic abnormalities. In general, information on the frequency of thrombotic events, their clinical characteristics and survival in adult patients with acute leukemia is still scarce and controversial. OBJECTIVES: To describe the frequency of thrombotic events, their clinical characteristics and survival of adult patients with acute leukemia at the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City. MATERIAL AND METHODS: A patient cohort, diagnosed and treated between October 2003 and December 2009, was retrospectively analyzed in terms of thrombotic events, frequencies and survival curves. RESULTS: We analyzed 181 patients with a median age of 33 years, 80 were female (44.2%). Fifteen cases with thrombosis (8.3%) were documented and in 53.3% of cases, they were related to the use of a central venous catheter. The median time to development of thrombosis was 92 days; 33.3% of events occurred during the first 30 days after diagnosis. The incidence of thrombosis in patients receiving L-asparaginase was 15%. Of the 15 patients with thrombosis, 27% were alive and without evidence of disease at last follow-up, and 73% had died; disease progression was the most common cause of death (81.8%). None of the thrombotic events had an impact on mortality. Median overall survival (OS) was 349 days. CONCLUSIONS: The incidence of thrombosis in this adult acute leukemia population is comparable to that reported in the literature. Only a third of cases occurred during the first month after diagnosis; however, 93.3% of patients developed a thrombotic event during the first year after the diagnosis of acute leukemia. All cases were symptomatic and central venous catheter-related thrombosis was the most frequent presentation in this group. Survival curves comparing patients with and without thrombosis were similar. Prospective studies are necessary in order to assess the risk factors fostering thrombosis in adult patients with acute leukemia.

A multicenter, open-label, noncomparative screening study of enzastaurin in adult patients with non-Hodgkin lymphomas.

PURPOSE: To assess the antitumor activity of enzastaurin in patients with non-Hodgkin lymphomas: T-cell lymphoma (n = 23): cutaneous and peripheral T-cell lymphoma; indolent B-cell lymphomas (n = 19): small lymphocytic, follicular grade 1 or 2, marginal zone lymphomas; and aggressive B-cell lymphomas (n = 15): follicular lymphomas grade 3, aggressive lymphoma with a clinical history. The primary objective was to determine overall tumor response. Secondary objectives included duration of response and safety. MATERIALS AND METHODS: In this multicenter, open-label, noncomparative, screening study conducted between December 2007 and February 2009, patients (≥ 18 years) who relapsed after ≥ 1 prior systemic treatment or who were intolerant to standard systemic therapy received 250 mg oral enzastaurin (125 mg tablets twice a day; a 1125-mg loading dose on day 1), in 28-day cycles for up to 2 years unless unacceptable toxicity or progressive disease occurred. RESULTS: Responses were seen in follicular lymphomas grade 3 (1/5, 20.0%), cutaneous T-cell lymphoma (2/11, 18.2%), small lymphocytic lymphomas (1/7, 14.3%), and aggressive lymphoma with a clinical history (1/10, 10.0%) in this heavily pretreated patient population (median prior therapies range from 4 to 10). Most drug-related toxicities were grade 1/2, the most common being diarrhea, peripheral edema, and pruritus. CONCLUSIONS: Enzastaurin was well tolerated but demonstrated modest responses across subgroups in this heavily pretreated patient population.

Diagnosis of acute leukemia in cerebrospinal fluid (CSF-acute leukemia).

Cerebrospinal fluid-acute leukemia (CSF-acute leukemia) is a frequent and serious complication in patients with acute leukemia. One of the major problems of this complication is the diagnosis process itself. CSF cytology is currently considered the gold standard for establishing the diagnosis, a technique which presents various processing limitations, seriously impacting the predictive values. In the last 11 years, studies of CSF flow cytometry analysis done in patients with acute leukemia have demonstrated superiority in comparison with CSF cytology. Although comparative studies between these two techniques have been reported since 2001, no new consensus or formal changes to the gold standard have been established for the CSF acute leukemia diagnosis. The evidence suggests that positive flow cytometry cases, considered as indeterminate cases, will behave like disease in the central nervous system (CNS). Nevertheless, we think there are some variables and considerations that must be first evaluated under research protocols before CNS relapse can be established with only one positive flow cytometry analysis in the setting of indeterminate CSF samples. This paper proposes a diagnostic algorithm and complementary strategies.

Thrombosis and acute leukemia.

Thrombosis is a common complication in patients with acute leukemia. While the presence of central venous lines, concomitant steroids, the use of Escherichia coli asparaginase and hereditary thrombophilic abnormalities are known risk factors for thrombosis in children, information on the pathogenesis, risk factors, and clinical outcome of thrombosis in adult patients with acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is still scarce. Expert consensus and guidelines regarding leukemia-specific risk factors, thrombosis prevention, and treatment strategies, as well as optimal type of central venous catheter in acute leukemia patients are required. It is likely that each subtype of acute leukemia represents a different setting for the development of thrombosis and the risk of bleeding. This is perhaps due to a combination of different disease-specific pathogenic mechanisms of thrombosis, including the type of chemotherapy protocol chosen, the underlying patients health, associated risk factors, as well as the biology of the disease itself. The risk of thrombosis may also vary according to ethnicity and prevalence of hereditary risk factors for thrombosis; thus, it is advisable for Latin American, Asian, and African countries to report on their specific patient population.

[Dermatoses in patients with acute myeloid and lymphoid leukemia. Cohort follow-up in a tertiary care hospital]. / Dermatosis en pacientes con leucemia aguda mieloide y linfoide. Seguimiento de una cohorte en un hospital de tercer nivel.

INTRODUCTION: Cutaneous manifestations in patients with acute leukemia (AL) cover a broad spectrum, including those due to leukemia per se, to chemotherapy and other drugs and those inherent to hospital care. MATERIAL AND METHODS: This is a cohort study in a tertiary hospital setting where the development of dermatoses was followed for 2 years in 22 patients with the diagnosis of AL. RESULTS: During the study, all patients developed some type of dermatosis, mostly due to chemotherapy.

[Acute myeloid leukemia in adults: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from 2003 to 2008]. / Experiencia del INCMNSZ en pacientes adultos con leucemia mieloide aguda. Cohorte 2003-2008.

INTRODUCTION: Acute myeloid leukemia (AML) comprises a group of diseases with different biologic characteristics; despite knowledge improvements, these are not reflected in long term survival. OBJECTIVE: To describe characteristics of adults with AML in a hospital of Mexico City, their treatment response, complications and to evaluate survival related factors. MATERIAL AND METHODS: Cohort study. Between January 2003 and July 2008, patients with AML diagnosis were included (except promyelocitic). Treatment protocols used: 3 + 7, high doses of cytarabine and autologous bone marrow transplant as consolidation therapy. RESULTS: 53 patients were included. Median age: 44 years (15-79). At diagnosis: tumor lysis syndrome in 4/ 53 (7.5%), 3/51 (5.9%) with altered liver function test and hyperleukocytosis in 8/53 (15.1%). 46 patients had available cytogenetic and this was successful in 28/46 (60.8%), 12/28 (42.8%) had adverse cytogenetic; 16/28 (57.1%) intermediate risk and none was favorable. There were 2 losses during follow up, 7 patients did not receive chemotherapy with curative intent and 1 died at diagnosis. 43 patients received 3 + 7, 13.9% died during aplasia, complete remission was achieved in 27/43 (62.7%) and 10/43 (23.2%) were refractory to treatment. A second induction attempt was required in 39.5% (17/43). Median disease free survival (DFS) was 491 days (366-615), with a median follow up of 993 days (105-1744). The median overall survival (OS) was 531 days (312-749). Aplasia related mortality decreased (p = 0.09) between the actual cohort (13.9%) and the historical cohort (37%). CONCLUSIONS: Long term survival in AML patients remains poor despite improvements in diagnosis, classification, and treatment. In our institution, it is required to improve induction protocols and cytogenetic analysis in order to adequately choose the group of patients that could be benefit from stem cell transplant.

Prospective evaluation of oral mucositis in acute leukemia patients receiving chemotherapy.

PURPOSE: Knowledge of oral mucositis (OM) in patients with acute leukemia (AL) and chemotherapy (CT) has remained limited. Thus, a prospective, longitudinal study was undertaken to characterize clinical features, associated risk factors, and behavior of OM in a cohort of AL patients starting CT. METHODS: Prospective and longitudinal study. A cohort of patients, older than 15 years of age with AL, scheduled to receive CT, was followed from March 2006 to October 2007. At baseline and three times per week, for 21 days, patients had an oral examination performed using the Oral Mucositis Assessment Scale (OMAS); also, oral pain and difficulty to swallow were recorded using a visual analog scale. Weekly, salivary flow measurements (Schirmer's test modified version) were done. RESULTS: A cohort of 29 AL patients was followed for a median time of 21 (range, 14-53) days; 12 (41.4%) developed OM, with a mean OMAS score of 0.181 (SD +/- 0.56) and a mean peak OMAS score of 1.8 (SD +/- 0.56). The OM onset mean time was 9.8 (range, 2-20, SD +/- 6.09) days, with a mean duration of 7 (range, 3-14, SD +/- 4.15) days. OM was significantly correlated with salivary flow [rs = 0.420 (P = 0.0051)], oral pain [rs = 0.47 (P < 0.0001)], ability to swallow [rs = 0.36 (P = 0.0001)], and type of food intake [rs = 0.38 (P < 0.0001)]. CONCLUSIONS: OM is a frequent and early side effect of CT closely correlated with oral pain, difficulty to swallow, and impairment in food intake.

Starch and albumin mixture as replacement fluid in therapeutic plasma exchange is safe and effective.

UNLABELLED: Therapeutic plasma exchange (TPE) is an effective treatment in Myasthenia gravis (MG) and Guillain-Barré syndrome (GBS) and 5% human albumin is the replacement fluid of choice; however, it is expensive. More recently, it has been suggested that starch is a safe and cheaper choice to human albumin. OBJECTIVE: To evaluate our 5-year experience using 3% hydroxyethyl starch (HES) and 5% human albumin mixture, as replacement fluid in TPE for these diseases. MATERIALS AND METHODS: Retrospective study carried out from January 2001 through September 2006. We included those patients with MG and GBS undergoing TPE. We analyzed clinical outcome (CO) and adverse events (AE) and our results were compared with a previous study which included similar patients undergoing TPE using just 5% human albumin. RESULTS: Thirty-one procedures were carried out in 26 patients, a total of 147 TPE sessions. In the group of MG we had 57% complete responses (CR) and 86% overall response (OR) while in the group of GBS we had 40% CR and 60% OR. When we analyzed our CO with the previous study no statistical differences were found. Mean processed plasma volume (PPV) was 4.2 in MG and 5.5 in GBS. Twenty patients had AE, being hypotension and catheter dysfunction the most frequent ones, while tachycardia, hypertension and paresthesias were statistically more frequent in the HES/albumin group. CONCLUSIONS: TPE with a mixture of 3% HES and 5% human albumin is as effective and safe as 5% human albumin alone for patients with these diseases.

[Acute lymphoblastic leukemia: experience in adult patients treated with hyperCVAD and 0195 Protocol, at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Cohort 2003-2007]. / Experiencia del INCMNSZ en pacientes adultos con leucemia linfoide aguda. Cohorte 2003-2007 con esquemas de tratamiento Hiper-CVAD y Protocolo 0195.

INTRODUCTION: Despite therapeutic advances, acute lymphoblastic leukemia (ALL) in adults remains a disease with poor long term outcome and survival rates. Developing countries lack of information about this disease. On the other hand, infections are frequent complications related to mortality and some research studies do not show accurate rates of septic shock or other related factors. OBJECTIVE: To describe characteristics of adults with acute lymphoblastic leukemia, response to treatment, complications and to evaluate further survival related factors and to compare our experience with other reports of literature. MATERIAL AND METHODS: Between September 2003 to November 2007, the entire cohort of patients with diagnosis of ALL was included. The treatment regimens used were MDACC HyperCVAD (HCVAD) and 0195 (institutional regimen). RESULTS: Of 40 patients included with the diagnosis of ALL, 92% was B phenotype and 8%, T phenotype, with a median age of 27 years. The median follow up was 28.5 months. Initially, 14% showed central nervous system infiltration; of 51% with available cytogenetics, 16.7% was Philadelphia chromosome positive. There were 36 patients who received treatment: 13 received HCVAD and 23 the 0195 protocol; 78% achieved global complete remission, 85% for the patients with HCVAD and 74% with 0195. The induction death rate was 2.8%. The median disease-free survival was 11.6 months (IC 95%, 2.5-20.8 months) and overall survival was 15 months (IC 95%, 10.6-19.4 months). In 95% of patients, no prophylactic antibiotic therapy was used and treatment related death was 8.4% (2.8% during induction and 5.6% during the rest of treatment). Factors associated with worse survival rate were hyperleukocytosis, T phenotype and lack of early complete remission. During induction, grade 3 to 4 non hematopoietic toxicity was 17%. Incidence of neutropenic febrile episodes was 61% and septic shock was 11%. CONCLUSIONS: With HCVAD, we observed worse complete remission, disease-free survival and overall survival rates compared with the original MDACC reports. Chemotherapy related death rates are similar to other early reports, despite prophylactic antibiotic was not used during myelosuppression.

[Fluoroquinolone prophylaxis utility during chemotherapy-induced severe neutropenia in patients with acute leukemia, with fluoroquinolone resistance high prevalence, in a reference hospital in Mexico City]. / Utilidad de la profilaxis con fluoroquinolonas durante la neutropenia grave inducida por quimioterapia en pacientes con leucemia aguda, en un hospital de referencia de la Ciudad de México con alta prevalencia de resistencia a fluoroquinolonas.

BACKGROUND: The use of fluoroquinolone prophylaxis in patients with cancer and neutropenia has failed to show a significant impact on mortality, despite its usefulness in reducing the incidence of gramnegative bacteremia. However, an increase in grampositive bacteremia and the emergence of resistant colonizing bacteria have consistently been noticed. OBJECTIVE: To determine the impact of prophylaxis with fluoroquinolones on the incidence of bacteremia and mortality in a hospital with high fluorquinolone resistance in Mexico City. PATIENTS: We conducted a retrospective and comparative study of patients with acute mieloid (AML) and hybrid (HL) leukemia who received or not prophylaxis with fluoroquinolones and who were attended from January 2000 to December 2003. We reviewed all pertinent clinical and laboratory data of the hematologic malignancies and the febrile episodes. RESULTS: A total of 108 febrile episodes of severe neutropenia occurred in 69 patients, with an incidence of 6.5 events/1000 day-patient with neutropenia. The median age was 35 +/- 18.3 years and 58% were men; 51 patients had AML (71.8%) and 20 (28.1%) HL. Prophylaxis had been given since the beginning of granulocytopenia in 46 (42.6%) febrile episodes (group 1), where as in 62 no prophylaxis was given (group 2). Of the 46 episodes with prophylaxis, 27 received ciprofloxacin 500 mg qd p.o. and 19, ciprofloxacin 500 mg qd po plus fluconazol 100 mg qd po. The median duration of prophylaxis was 8.5 days (range 1-90 days). Twenty-nine bacteremias (26.8%) were documented, with an incidence of 16.4 bacteremias/1000 day-patient with neutropenia, 12 (26%) in group 1 and 17 (27.5%) in group 2. Bacteremia was most frequently caused by gram negative organisms (18/29), being Escherichia coli (14) the most commonly isolated pathogen, with 7 episodes in each group. Eight (29.6%) of the 21 isolates in which fluoroquinolone susceptibility was tested were ciprofloxacin resistant, 3 in group 1 and 5 in group 2 (p = 0.58). Median survival of patients was 38 days in group 1 and 40 days in group 2. (p = 0.2); mortality was similar in both groups, 34% and 27%, respectively. CONCLUSIONS: In a hospital with a high prevalence of fluoroquinolone-resistance, prophylaxis in patients with acute leukemia and severe neutropenia did not prevent febrile episodes and did not have any impact on mortality. However, there was no increase in infections caused by resistant bacteria.