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Introduction: The impact of an admission to ICU before stem cell transplantation (SCT) on post-SCT outcome is not well established., Patients and Methods: We reviewed the medical records of patients who had received a first SCT between 2000 and 2016 in our institution. The outcome of 22 patients who required ICU admission during chemotherapy prior to SCT (ICU group) was compared with 44 matched patients (1:2) who did not need it (NO-ICU group)., Results: There were no differences in transplant complications, in time to neutrophil and platelet recovery or in the length of hospital stay during SCT between the ICU and NO-ICU groups. However, microbiologically documented infections were more common in the ICU group (16/20) than in the NO-ICU group (18/39) (p=.027). The 5-yr overall survival probability (CI 95%) was 49% (28-70%) in the ICU vs. 45% (29-61%) in the NO-ICU group (p=.353), while the 5-yr incidence of non-relapse mortality was 32% (14-52%) and 24% (12-38%) (p=.333), respectively. Six patients (27%) in the ICU group and 8 (18%) in the NO-ICU group required admission to the ICU during or after the SCT procedure (p=.293). Twelve (54%) patients in the ICU and 22 (50%) in the NO-ICU group died, the causes of death were similar in both groups., Conclusion: Our results show that admission to the ICU prior to SCT does not have a negative impact on patient outcomes following SCT and should not be considered as an exclusion criterion for SCT., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Patients submitted to haematopoietic stem cell transplantation (HSCT) are at increased risk of late complications, such as second neoplasm (SN). The incidence and risk factors of SN in patients receiving HSCT at a single centre were analysed., Patients and Methods: The follow-up of adult patients who received a first HSCT (autologous [auto-HSCT] or allogeneic [allo-HSCT]) between January 2000 and December 2015 was reviewed. We collected their demographic characteristics, the primary disease and type of HSCT, and analysed the cumulative incidence of SN and their risk factors., Results: Of 699 transplanted patients (auto-HSCT, n=451; allo-HSCT, n=248), 42 (6%) developed SN (17 haematological and 25 solid), 31 post-auto-HSCT and 11 post-allo-HSCT. Haematologic SN were more frequent after auto-HSCT than after allo-HSCT. The median time between HSCT and SN was 4.09 years [range 0.07-13.15], with no differences between auto-HSCT and allo-HSCT. The cumulative incidence of SN was 5% (95% CI 3-6) at 5 years, 7% (95% CI 5-10) at 10 years and 11% (95% CI 8-15) at 15 years, without differences according to the type of HSCT. Only the age over 40 years correlated with an increased risk of SN., Conclusions: In this series, the incidence of post-HSCT SN was similar to that previously described. Patients submitted to an auto-HSCT showed a higher frequency of haematologic SN. A higher incidence of SN was detected in patients older than 40 at the time of HSCT., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Background: The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab., Patients and Methods: We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy., Results: Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival)., Conclusion: In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL., Patients and Methods: We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy., Results: The most frequent CNA were alterations in the 14q32.33 region (11 cases, 44%) followed by alterations in the cell cycle regulator genes CDKN2A/B and RB1 (16%). No correlation between the presence of specific CNA and the clinical-biologic features or the response to therapy was found., Conclusions: The high frequency of CNA in the 14q32.33 region, CDKN2A/B and RB1 found in our study could contribute to the aggressiveness and invasiveness of mature B-ALL., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Background and Purpose: Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients., Patients and Method: Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received., Results: Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P=.001) and overall survival (4.5 [1.2-17.8], P=.03)., Conclusions: In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients do not achieve the optimal response or are resistant to TKI. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Treatment with second-generation TKI has produced high rates of hematologic and cytogenetic responses in mutated ABL patients. The aim of this study was to determine the type and frequency of ABL mutations in patients who were resistant to imatinib or had lost the response, and to analyze the effect of second-generation TKI on their outcome., Patients and Methods: The presence of ABL mutations in 45 CML patients resistant to imatinib was evaluated by direct sequencing and was correlated with the results of the cytogenetic study (performed in 39 cases). The outcome of these patients after therapy with nilotinib or dasatinib was analyzed., Results: ABL mutations were detected in 14 out of 45 resistant patients. Patients with clonal cytogenetic evolution tended to develop mutations more frequently than those without clonal evolution. Nine out of the 15 patients with ABL mutation responded to a treatment switch to nilotinib (n=4), dasatinib (n=2), interferon (n=1) or hematopoietic stem cell transplantation (n=2)., Conclusion: The frequency of ABL mutations in CML patients resistant to imatinib is high and is more frequent among those with clonal cytogenetic evolution. The change to second-generation TKI can overcome imatinib resistance in most of the mutated patients., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Background and Objective: Patients with hematological neoplasms transferred to an Intensive Care Unit (ICU) for a life-threatening complication have a poor outcome. In these patients, it is crucial to identify clinical and biologic parameters with potential prognostic significance. This study prospectively evaluated the usefulness of serum procalcitonin (PCT) levels as a predictor of complications (infectious or not) and outcome in these patients., Patients and Method: One hundred patients with hematological malignancy were admitted to the ICU from October 2004 until August 2009. In 59 of them serum PCT levels were daily measured from the ICU admission until a maximum period of 10 consecutive days., Results: Hematological diseases were acute leukemia (n=30), lymphoma and other lymphoproliferative disorders (n=18), multiple myeloma (n=7) and other (n=4). Twenty-five patients (42%) had received hematopoietic stem cell transplantation. Thirty-seven patients (63%) presented neutropenia. Those patients who could not be discharged alive from the ICU presented higher PCT levels on days 1, 2 and 3. PCT levels were significantly higher in those patients with neutropenia or septic shock or other causes of hemodynamic instability. The presence of a microbiologically documented infection, respiratory failure or the need of mechanical ventilation support did not significantly affect PCT levels in this study., Conclusions: Early serum PCT levels measurement might be useful for predicting mortality in patients with hematological malignancy requiring advanced life support., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Background and Objective: The growing use of antineoplastic treatments has led to an increase in the incidence of therapy-related leukemias (TRL). The objective was to describe the characteristics of TRL., Patients and Methods: Twenty-three cases of TRL were registered. Chemotherapeutic agents used for the first tumor, time interval, clinical and biological characteristics, treatment and prognosis of the TRL were analyzed., Results: Median age was 61 years. Cytotoxic agents used in previous neoplasm consisted of alkylating agents (17 patients), inhibitors of DNA topoisomerase II (14), antitubulin agents (12), radiotherapy (9, in 6 with radiotherapy) and antimetabolites (6). Median time from diagnosis of the first neoplasm to TRL was 3 years (range 1.2-15.8). Thirteen patients received intensive chemotherapy [with stem cell transplantation (SCT) in 3] and the other 10 received symptomatic treatment (median survival 3 years versus 0.079 years, P=0.004)., Conclusions: In this study, TRL were associated with exposure to alkylating agents, antitubulin agents and topoisomerase II inhibitors. Response to treatment and prognosis were poor, although chemotherapy and SCT may prolong survival., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Background and Objective: Severe acute graft versus host disease (GVHD) and extensive chronic GVHD not responding to steroids have poor prognosis. Infliximab has reported to be effective in some of these patients. The efficacy of infliximab for the treatment of patients with steroid-resistant GVHD was evaluated., Patients and Methods: Retrospective analysis to evaluate the activity and toxicity of infliximab in 9 patients with acute or chronic steroid resistant GVHD., Results: Six patients had acute GVHD and 3 chronic GVHD. The source of progenitors was peripheral blood in all patients except one. Six received matched-related SCT and 3 unrelated SCT. Patients received between 2 and 7 doses of infliximab, and 5 achieved a partial response. All patients presented infections: 4 developed Pseudomonas aeruginosa septicemia and 5 probable or confirmed infection by Aspergillus fumigatus., Conclusions: Infliximab provides transient response in steroid-resistant GVHD. However, it is associated with a high rate of infections. Earlier administration of infliximab should be explored to reduce the frequency of infections., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Background and Objectives: To assess the use of the Epstein-Barr virus (EBV) viral load as a marker for lymphoma diagnosis in HIV-infected patients. We also aimed to identify the relationship between EBV viral load in plasma and the presence of EBV in lymphoma cells., Patients and Methods: Retrospective observational study of two HIV-infected populations: one of patients diagnosed with lymphoma and a control group. Thirty-nine patients with AIDS-related lymphoma (ARL) (32 non-Hodgkin's and 7 Hodgkin's lymphomas) and 134 HIV-positive individuals without neoplasia or opportunistic infections were studied. Blood samples were collected before lymphoma treatment in ARL patients. EBV viral load was measured in plasma by real-time quantitative PCR and the presence of EBV-EBER mRNA in lymphoma tumor was investigated by in situ hybridization., Results: Patients with ARL had higher EBV viral loads than those without lymphoma: 24,180.5 (±73,387.6)copies/mL versus 2.6 (±21.6)copies/mL (p<0.001). HIV-infected patients without lymphoma had negative or very low EBV load values. Among ARL patients, no correlation was found between EBV viral loads and CD4+ lymphocyte counts or between EBV and HIV RNA loads, or any other clinical or biological parameter. Cases with an EBV-EBER-positive lymphoma had higher EBV viral loads than those with EBER-negative tumors., Conclusions: EBV viral load is a useful marker of lymphoma in HIV-infected patients, and may be a useful tool for early diagnosis and treatment., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

With the widespread use of highly active antiretroviral therapy (HAART) the incidence of systemic non-Hodgkin lymphoma (NHL) in patients infected with the Human Immunodeficiency Virus (HIV) has declined. HAART has also modified the clinical manifestations of these tumors, with a lower frequency of involvement of the central nervous system (CNS). Currently, the frequency of meningeal involvement at the time of diagnosis of NHL in HIV-infected patients varies between 3% and 5%. These figures are similar to those observed among immunocompetent hosts. The diagnosis of meningeal lymphoma relies in clinical findings, imaging techniques, and cerebrospinal fluid (CSF) examination. Flow cytometry is a diagnostic technique with a higher sensitivity and specificity than conventional cytology for the diagnosis of meningeal lymphoma. However, flow cytometry is not yet considered to be the gold standard for this purpose. Until recently, most experts recommended neuromeningeal prophylaxis for all HIV-infected patients with aggressive NHL. However, at present this prophylaxis is recommended only in patients with higher risk of CNS relapse according to different sites of involvement, stage and histological subtype. There are different regimens of prophylaxis and treatment for meningeal lymphoma. The drugs most commonly used for this purpose are methotrexate and cytosine arabinoside. However, there are other alternatives such as liposomal cytosine arabinoside that requires fewer spinal taps for drug administration and whose results are very promising. In summary, in the context of an effective HAART, HIV infected patients with NHL have a frequency of CNS involvement by lymphoma similar to that found among immunocompetent hosts. Consequently, indications and regimens for CNS prophylaxis in HIV-infected patients with NHL should not be different than those employed in the general population. Universal CNS prophylaxis should be reserved for the few patients unable to receive an effective HAART., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Background and Objective: Central nervous system (CNS) involvement in patients diagnosed with non-Hodgkin's lymphoma (NHL) or other lymphoproliferative disorders is an infrequent complication with a poor prognosis. The prophylaxis and treatment of CNS involvement in these patients are not homogenous. The aim of this prospective longitudinal study was to report the current practice of CNS prophylaxis and treatment in patients with lymphoproliferative disorders in Spain., Methods: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr) diagnosed with NHL or other lymphoproliferative disorders who received CNS prophylaxis or treatment were consecutively included through online registration., Results: 228 patients from 33 hospitals were included. The mean (SD) age was 52 (16) yr and 144 (63%) were males. CNS therapy was given to 41 cases and consisted of triple intrathecal (IT) therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 22, liposomal depot cytarabine in 18 and methotrexate in one. In addition, 4 patients received cranial radiotherapy. CNS prophylaxis (n = 187) consisted of TIT (166 cases), IT methotrexate (17), IT liposomal depot cytarabine (3) and IT cytarabine (1), whereas cranial or craniospinal radiotherapy was administered to 2 patients. The main reasons for CNS prophylaxis cited by the investigators included extranodal involvement (89 patients), raised serum lactate dehydrogenase level (87), IPI score > 2 (62), bulky mass (43), extranodal involvement in more than one organ (33), age over 60 yr (28) and human immunodeficiency virus infection (13)., Conclusions: The results of this study point out the generalized use of TIT therapy both for CNS prophylaxis and therapy in patients with lymphoproliferative disorders in Spain. The introduction of the new formulations of drugs, especially liposomal depot cytarabine for CNS involvement, and the scarce use of radiotherapy are also of note. Similar to other studies, the absence of homogeneous criteria for CNS prophylaxis is of note.

Background and Objective: Central nervous system (CNS) involvement in patients diagnosed with acute leukemias (AL) is an uncommon complication with poor prognosis. The indication and the schedules of prophylaxis and treatment of CNS involvement in AL are not homogenous among countries and within the same country. The aim of this prospective longitudinal study was to analyze and report the practice of CNS prophylaxis and treatment in patients with AL in Spain., Patients and Method: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr.) diagnosed with AL who received CNS prophylaxis or treatment were consecutively included through online registration., Results: 265 patients from 32 hospitals were included. Mean (standard deviation) age was 44 (16) yr. and 133 (50%) were males. For acute lymphoblastic leukemia patients (n = 158), CNS therapy was given to 12 cases (10 at diagnosis and 2 at relapse) and consisted of triple intrathecal therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 11 and liposomal depot cytarabine in one. CNS prophylaxis (n = 146) consisted of TIT in 135 cases, intrathecal methotrexate in 7, intrathecal cytarabine in 2 and intrathecal liposomal depot cytarabine in 2. No cranial irradiation either for prophylaxis or therapy was given in any case. In acute myeloblastic leukemia patients (n = 107), CNS therapy was administered to 17 cases (9 at diagnosis and 8 at relapse). Intrathecal therapy consisted of TIT in 11, intrathecal liposomal depot cytarabine in 5 and intrathecal cytarabine in one. One patient also received craniospinal irradiation. CNS prophylaxis (n = 90) consisted of TIT in 68 cases and intrathecal methotrexate in 22., Conclusions: In Spain, the patterns of CNS prophylaxis and therapy for AL are homogeneous. TIT was the most frequent schedule for CNS prophylaxis and therapy. The lack of use of cranial or craniospinal irradiation and the administration of new drugs (i.e.: liposomal depot cytarabine) for CNS therapy and prophylaxis is of note.

Background and Objective: There is scarce information on the influence of stem cell transplantation (SCT) on the prognosis of patients with hematological malignancies admitted to an intensive care unit (ICU)., Patients and Method: The mortality during ICU admission, long-term survival and the prognostic factors for survival were analyzed and compared in transplanted vs. non-transplanted patients., Results: 116 critically-ill patients with a hematological malignancy transferred to the ICU in a single institution were analyzed. Thirty patients had received SCT prior to ICU admission. Transplanted and non-transplanted patients were comparable for demographic variables (except age and disease status) and reasons for ICU admission. No differences were found in overall survival or survival after discharge from ICU between transplanted and non-transplanted patients. Thirty-nine out of 85 non-transplanted patients (46%) and 11 out of 31 transplanted patients (35%) could be discharged from the ICU. The prognostic factors for survival in non-transplanted patients were need of mechanical ventilation or cardiovascular vasoactive drugs. However, only the liver function impairment predicted the outcome in the transplanted patients through the multivariate analysis., Conclusions: A significant proportion of patients admitted to ICU were discharged despite previous SCT. These patients did not have a worse prognosis than those transferred to the ICU with a hematologic malignancy, although the prognostic factors for survival were different in the 2 groups of patients.

Background and Objective: Several groups have used salvage chemotherapy in relapsed or refractory lymphomas to mobilize peripheral blood stem cells. The objective of this study was to evaluate the antilymphomatous efficacy, the ability of mobilization and the toxicity of a regimen containing high-dose ifosfamide, etoposide, methylprednisolone (IFOVM) and granulocyte colony-stimulating factor (G-CSF)., Patients and Method: Twenty-four patients with relapsed or refractory lymphoma received IFOVM and G-CSF. The median age was 45 years and 13 were males. The histologyc subtypes of lymphoma were: diffuse large B cell (DLBCL) (n = 15), Hodgkin (n = 2), Burkitt (n = 2), mantle cell (n = 2), anaplastic (n = 1), peripheral T-cell (n = 1) and follicular (n = 1)., Results: Two patients died of sepsis within the pancytopenia period. In 17 (77%) of the remaining patients more than 1.5 x 10(6) CD34+ cells/kg (median: 7.7 x 10(6) CD34+ cells/kg) were collected. The median time to peripheral blood stem cells harvest was 17 (range: 13-24) days and 4 patients required 2 procedures of apheresis. Sixteen patients (67%) developed neutropenic fever. The median time to achieve granulocyte cell count > 1 x 10(9)/l and platelet count > 20 x 10(9)/l was 15 and 16 days, respectively. The only factor predicting successful mobilization was the diagnosis of DLBCL (p = 0.04). Ten patients underwent peripheral blood stem cells transplantation., Conclusions: The regimen IFOVM and G-CSF allows an effective peripheral blood stem cells mobilization in patients with lymphoma, particularly in those with DLBCL, but it is associated with significant toxicity.

Background and Objective: Neutropenic enterocolitis (NE) is a complication arising in neutropenic patients with acute leukemia or solid tumours while treated with intensive chemotherapy. The optimal therapeutic procedures have not been well established., Patients and Method: Seven cases of NE diagnosed and treated in a tertiary hospital between 2000 and 2007 are described. Their clinico-biological characteristics, therapeutic procedures and evolution were analysed retrospectively., Results: Five of the patients were males, their median age was 39 years. Acute myeloblastic leukemia was the most frequent diagnosis (5 cases). Two other patients had received an stem cell transplantation. Abdominal pain was present in all patients, diarrhoea in 6, and fever in 5. Microorganisms were isolated from blood cultures in 4 cases (Clostridium septicum, Escherichia coli, Pseudomonas aeruginosa and Aeromonas hydrophila). Abnormal mural thickening of the caecum was observed in the 6 cases in which a computed tomography scan could be performed. The median mural thickness at its maximum section was 11 mm (range: 8-16). All patients first received medical treatment with wide spectrum antibiotics and intestinal rest, and abdominal surgery was indicated in 6 cases after a median time from first symptom of 4 days (range: 0-12). NE was confirmed histologically in all 6 patients. Five patients required admission in Intensive Care Unit and 2 (29%) died as a result of NE., Conclusions: NE is a severe complication of patients with hematologic malignancies submitted to intensive chemotherapy or receiving stem cell transplantation. Abdominal computed tomography scan is the most valuable diagnostic tool. Prompt surgical intervention may improve the prognosis in patients with NE.