Juan-Manuel Sancho

Outcome and prognostic factors in patients with hematologic malignancies admitted to the intensive care unit: a single-center experience.

Patients who are admitted to the intensive care unit (ICU) with hematologic malignancies have a poor prognosis, although outcomes have improved in recent years. This study analyzed ICU mortality, short- and long-term survival, and prognostic factors for 100 consecutive critically ill patients with a hematologic malignancy who were admitted to our polyvalent ICU from January 2000 to May 2006. The median age was 55 years (range, 15-75 years; male-female ratio, 60:40). The main acute life-threatening diseases precipitating ICU transfer were respiratory failure (45 patients, 45%) and septic shock (33 patients, 33%). Forty-two patients (42%) were discharged from the ICU.The ICU mortality rate from 2004 to 2006 was lower than from 2000 to 2003 (49% versus 69%,P < .047).The 1- and 2-year probabilities of survival for patients discharged from the ICU were 67% (95% confidence interval [CI], 51%-84%) and 54% (95% CI, 34%-73%), respectively. A multivariate analysis revealed hemodynamic instability (odds ratio, 2.11; 95% CI, 1.17-3.83;P = .014) and mechanical ventilation (odds ratio, 4.27; 95% CI, 1.70-10.74;P = .002) to be the main predictors of a poor survival prognosis. Almost half of patients with hematologic malignancy and life-threatening complications can be discharged from the ICU. Age and underlying disease characteristics do not influence ICU outcome, which is mainly determined by hemodynamic and ventilatory status.

Results of the PETHEMA ALL‐96 trial in elderly patients with Philadelphia chromosome‐negative acute lymphoblastic leukemia

Background and aim: Only 20–30% of elderly patients with acute lymphoblastic leukemia (ALL) are enrolled in clinical trials because of co‐morbid disorders or poor performance status. We present the results of treatment of Philadelphia chromosome‐negative (Ph−) ALL patients over 55 yr treated in the PETHEMA ALL‐96 trial. Patients and methods: From 1996 to 2006, 33 patients 55 yr with Ph− ALL were included. Induction therapy was vincristine, daunorubicin, prednisone, asparaginase, and cyclophosphamide over 5 weeks. Central nervous system (CNS) prophylaxis involved triple intrathecal (IT) therapy, 14 doses over the first year. Consolidation‐1 included mercaptopurine, methotrexate, teniposide and cytarabine, followed by one consolidation‐2 cycle similar to the induction cycle. Maintenance consisted of mercaptopurine and methotrexate up to 2 yr in complete remission (CR) with monthly reinduction cycles (vincristine, prednisone and asparaginase) during the first year. Results: Median (range) age was 65 yr (56–77). Phenotype (30 patients): early‐pre‐B 7, common/pre‐B 18, T 5. Cytogenetics (28 patients): normal 12, complex 10, t(4;11) 2 and other 4. CR was achieved in 19/33 (57.6%) patients, early death occurred in 12 (36.4%) and 2 (6%) were resistant. Overall survival and disease‐free survival probabilities (2 yr, 95% CI) were 39% (21%–57%) and 46% (22%–70%), respectively (median follow up of 24 months). Removal of asparaginase and cyclophosphamide from the induction decreased induction death (OR 0.119, CI 95% 0.022–0.637, P = 0.013) and increased survival (20% vs. 52%, P = 0.05). Conclusions: The prognosis of elderly Ph− ALL patients is poor. In this study, less intensive induction decreased toxic death, allowing delivery of planned consolidation therapy and increased survival probability.

Clinical significance of occult cerebrospinal fluid involvement assessed by flow cytometry in non-Hodgkin’s lymphoma patients at high risk of central nervous system disease in the rituximab era

Background and aim:  Flow cytometry (FCM) analysis of cerebrospinal fluid (CSF) is more sensitive than conventional cytology (CC) for diagnosis of lymphomatous meningeosis, but the clinical significance of occult central nervous system (CNS) disease (positive FCM with negative CC) remains unknown.

Predictive factors for poor peripheral blood stem cell mobilization and peak CD34+cell count to guide pre-emptive or immediate rescue mobilization

BACKGROUND AIMS Failure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilization. METHODS Data from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 10(6) CD34(+)cells/kg body weight (BW). RESULTS The median age was 53 years (range 4-70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkins lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkins lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte-colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34(+)cell count in PB > 13.8/μL was enough to ensure ≥ 2 × 10(6) CD34(+)cells/kg, with high sensitivity (90%) and specificity (91%). CONCLUSIONS The prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34(+) cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization.

Acute Promyelocytic Leukemia in a HIV Seropositive Patient

Acute myeloid leukemia (AML) is infrequent in patients with human immunodeficiency virus (HIV) infection. Among AML, acute promyelocytic leukemia (APL) has been rarely described in such patients, with only one case being published. We report a 30 years-old intravenous drug abuser HIV-infected male with APL who attained complete clinical, morphological, and molecular remission after differentiation therapy with all-trans-retinoic acid (ATRA) followed by intensive chemotherapy. The results of treatment in this patient and in other AML published cases suggest that therapy for AML should not be modified because of HIV infection if patients have an adequate performance status.

Translocation (3;8)(q27;q24) in two cases of triple hit lymphoma.

Unclassifiable lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma is a new category of B-cell lymphoma appearing in the new World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements. According to the presence of two or three rearrangements, these lymphomas are called double-hit lymphomas or triple-hit lymphomas (THL), respectively. Here we report two cases of THL with MYC, BCL2, and BCL6 rearrangements and t(3;8)(q27;q24) diagnosed in one center in the last two years.

Contribution of cerebrospinal fluid sCD19 levels to the detection of CNS lymphoma and its impact on disease outcome

Flow cytometry (FCM) is more sensitive than conventional cytology for detection of occult leptomeningeal lymphoma; however, some FCM-negative patients show central nervous system (CNS) recurrence. Here, we evaluated the cerebrospinal fluid (CSF) levels of 13 B-cell-associated markers and their contribution to the diagnosis of CNS lymphoma in 91 diffuse large B-cell lymphomas (DLBCL) and 22 Burkitt lymphomas (BLs). From all markers tested, CD19 was the most informative. Thus, higher soluble CD19 (sCD19) levels were associated with a greater frequency of neurological symptoms in DLBCL and BL and with parenchymal CNS lymphoma in DLBCL; sCD19 emerged as a powerful predictor of event-free and overall survival in DLBCL and BL, particularly when combined with FCM detection of CNS disease. These results support the utility of combined FCM detection of lymphoma cells and assessment of sCD19 levels in CSF, for more accurate identification of CNS disease in DLBCL and BL patients.

MYC protein expression is associated with poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

MYC and BCL2 gene translocations and protein expression have recently demonstrated to be of prognostic significance in systemic diffuse large B‐cell lymphoma (DLBCL). However, their role in primary central nervous system DLBCL (CNS‐DLBCL) prognosis has been scarcely analyzed. We studied the immunophenotype, the status of the MYC, BCL2, and BCL6 genes and the clinical features of a series of 42 CNS‐DLBCL and evaluated their prognostic significance. We found high MYC protein expression in 43% of cases, and this was associated with lower overall survival (OS). Cases with concurrent expression of MYC and BCL2 showed a lower OS, although the difference did not reach statistical significance. Translocations involving the MYC or BCL2 genes were not detected. The BCL6 gene was frequently translocated, but was unrelated to survival. We conclude that MYC protein expression detected by immunohistochemistry identifies a CNS‐DLBCL subset with worse prognosis and may contribute to a more accurate risk stratification of CNS‐DLBCL patients.

Results of Compassionate Therapy with Intrathecal Depot Liposomal Cytarabine in Acute Myeloid Leukemia Meningeosis

Intrathecal (IT) depot liposomal cytarabine is useful in solid tumors or lymphomatous meningitis, but has scarcely been used in central nervous system (CNS) involvement in acute leukemia. We report the results of compassionate therapy with IT depot liposomal cytarabine in 10 patients with acute myeloid leukemia with CNS involvement. Five of 6 cases receiving this drug as the only IT therapy and the remaining 4 receiving it as adjuvant therapy to other CNS-directed therapies showed clearance of cerebrospinal fluid blast cells, with sustained response in 5 and mild side effects. Systemic therapy was given concomitantly in all cases, with high-dose cytarabine in 6. Clinical trials should establish the role of IT liposomal cytarabine in leukemic meningitis.

HIV-infection impact on clinical-biological features and outcome of diffuse large B-cell lymphoma treated with R-CHOP in the combination antiretroviral therapy era.

Objective:Since the introduction of combination antiretroviral therapy (cART) patients with HIV-related diffuse large B-cell lymphoma (DLBCL) show better control of immunosuppression, which may have an impact on the characteristics and prognosis of the disease. We aimed to compare the clinical presentation and prognosis of patients with HIV-related and HIV-unrelated DLBCL treated with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) in the cART era. Methods and design:Eighty-one HIV-infected patients included in a Spanish multicentre trial were compared with 84 HIV-uninfected patients diagnosed in a Spanish institution in the same period all treated with R-CHOP. Results:HIV-infected patients had a worse performance status, more frequent B-symptoms, and higher Ann-Arbor stages than HIV-uninfected patients, with similar frequency of extranodal involvement. The complete response (CR) rate of patients with high tumor burden was not different in HIV-infected and HIV-uninfected patients. Patients with HIV-related DLBCL showed a worse overall survival (OS) (5-year OS: 56 vs. 74%) but a similar disease-free survival (DFS) (5-year DFS: 84 vs. 73%). In the subgroup of patients with high tumor, the results regarding survival were similar to the whole series. Previous AIDS-defining illness was the strongest negative prognostic factor for OS in HIV-infected patients. Conclusion:In the cART era, HIV-related DLBCL still presents more aggressive features than HIV-unrelated DLBCL, and has a worse OS despite having a similar DFS. Prevention of HIV-related complications is essential to achieve outcomes comparable with HIV-uninfected patients with DLBCL.