[Leukemia cutis: clinical features of 27 mexican patients and a review of the literature]. / Leucemia cutis (LC): características clínicas de 27 pacientes mexicanos y una breve revisión de la literatura.

BACKGROUND: Leukemia Cutis (LC) consists in neoplastic leukocytic infiltration of the skin and is strongly associated with the presence of extramedullary disease and poor prognosis. However, there are few studies in the literature regarding this entity. We perform a retrospective study of 27 mexican patients in order to analyze the clinical features and prognosis of LC in Mexico, and a brief review of the literature. METHODS: Cases diagnosed as LC by skin biopsy were selected from the database of the Department of Dermatology of National Institute of Medical Science and Nutrition Salvador Zubirán. Cases were searched between the dates of January 1993 and December 2013. RESULTS: Twenty-seven cases which were histologically confirmed with cutaneous leukemic infiltrate were included. Of these patients 60% were male and the mean age at diagnosis was 42 yr (19 to 80 yr). The predominant tipe of LC was acute myeloid leukemia (AML) with 48% of the cases. Nodular neoformations were the main clinical manifestation with 63% of the cases. The mean interval between the diagnosis of LC and death was 10 months (CI 95%). CONCLUSIONS: The presence of LC is a marker of poor prognosis and can precede the relapse of systemic leukemia. Cutaneous infiltration may be the first or the only sign of progression, so doctors should be familiar with the clinical manifestations of this disease.

Nijmegen breakage syndrome (NBS) as a risk factor for CNS involvement in childhood acute lymphoblastic leukemia.

Central nervous system (CNS) involvement is an independent risk factor for poor event-free survival and relapse confined to the CNS. Knock-out mice deprived of RAG2, the protein involved in DNA repair, developed leukemic infiltration within leptomeninges. Therefore, we hypothesized that DNA repair deficiencies in humans, such as Nijmegen breakage syndrome (NBS), may constitute a risk factor for CNS dissemination of acute lymphoblastic leukemia (ALL). Having analyzed the incidence of CNS2/CNS3 status at diagnosis of ALL in two independent cohorts from the Polish Pediatric Leukemia/Lymphoma Study Group, we noticed that among children with NBS CNS involvement was significantly frequent.

Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report.

Neurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%. It occurred as the initial manifestation of malignancy in 26% of cases. The affected neural structures included peripheral nerves (60%), spinal nerve roots (48%), cranial nerves (46%), and plexus (40%) with multiple site involvement in 58%. Imaging studies often suggested the diagnosis with 77% positive magnetic resonance imaging, and 84% (16 of 19) positive computed tomography-positron emission tomography studies. Cerebrospinal fluid cytology was positive in 40%, and nerve biopsy confirmed the diagnosis in 23 of 26 (88%). Treatment in 47 patients included systemic chemotherapy (70%), intra-cerebrospinal fluid chemotherapy (49%), and radiotherapy (34%). Response to treatment was observed in 46%. The median overall survival was 10 months, with 12- and 36-month survival proportions of 46% and 24%, respectively. NL is a challenging diagnosis, but contemporary imaging techniques frequently detect the relevant neural invasion. An aggressive multimodality therapy can prevent neurologic deterioration and is associated with a prolonged survival in a subset of patients.

Neurologic complications associated with intrathecal liposomal cytarabine given prophylactically in combination with high-dose methotrexate and cytarabine to patients with acute lymphocytic leukemia.

Central nervous system (CNS) prophylaxis has led to a significant improvement in the outcome of patients with acute lymphocytic leukemia (ALL). Liposomal cytarabine (Enzon Pharmaceuticals, Piscataway, NJ; Skye Pharma, San Diego, CA), an intrathecal (IT) preparation of cytarabine with a prolonged half-life, has been shown to be safe and effective in the treatment of neoplastic meningitis. Liposomal cytarabine was given for CNS prophylaxis to 31 patients with newly diagnosed ALL. All patients were treated concurrently with hyper-CVAD chemotherapy (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) including high-dose methotrexate (MTX) and cytarabine on alternating courses. Liposomal cytarabine 50 mg was given intrathecally on days 2 and 15 of hyper-CVAD and day 10 of high-dose MTX and cytarabine courses until completion of either 3, 6, or 10 IT treatments, depending on risk for CNS disease. Five patients (16%) experienced serious unexpected neurotoxicity, including seizures, papilledema, cauda equina syndrome (n = 2), and encephalitis after a median of 4 IT administrations of liposomal cytarabine. Toxicities usually manifested after the MTX and cytarabine courses. One patient died with progressive encephalitis. After a median follow-up of 7 months, no isolated CNS relapses have been observed. Liposomal cytarabine given via intrathecal route concomitantly with systemic chemotherapy that crosses the blood-brain barrier such as high-dose MTX and cytarabine can result in significant neurotoxicity.

Clinical presentations and complications of hairy cell leukemia.

HCL typically presents in middle-aged men, and is characterized by splenomegaly and cytopenias. Hepatomegaly may be present, but it usually is not a salient feature. Peripheral adenopathy is uncommon. Other organ manifestations occur, but are unusual. patients are now presenting with a less tumor burden, as a result of earlier diagnosis. Leukocytosis/lymphocytosis should suggest HCl variant. Infectious complications, which were common in the past and the major cause of death, have become rare in the era of purine analog therapy. Whether there is a true increased risk for second malignancies remains controversial.

Clinical tumor cell distribution pattern is a prognostically relevant parameter in patients with B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: B-cell chronic lymphocytic leukemia (B-CLL) cells are variably distributed among the major lymphoid compartments contributing to the heterogeneous clinical presentation and course of this disease. In order to evaluate this variable distribution we propose a model for its clinical assessment. DESIGN AND METHODS: We introduce the model for tumor distribution (TD) assessment based on TTM scoring system, where TD value represents percentage of total tumor mass infiltrating peripheral blood and bone marrow (TD=TM(1)/TTM). TD in B-CLL can be categorized into 3 subgroups: pure leukemia if TD=100%, predominantly leukemia if TD=50-99% and predominantly lymphoma TD<50%. RESULTS: Among 341 B-CLL patients there were 22.6%, 55.1%, 22.3%, pure leukemia, predominantly leukemia and predominantly lymphoma cases, respectively. TD parameter was strongly associated in univariate analysis with TTM size, Rai and Binet stages, spleen size and beta(2) microglobulin. TD was associated with response to therapy and survival, with higher TD values translated into higher response rates and longer survival. However, in univariate and multivariate Cox analysis TD displayed much stronger relationship with prognosis in female patients, where it is the strongest independent predictor of survival along with age and Binet stage. INTERPRETATION AND CONCLUSIONS: TD, a quantitative and simple clinical parameter, easily assessed in all patients, offers a reliable tool for evaluation of tumor cell distribution in B-CLL. It has independent and strong prognostic power in females, as opposed to males, possibly unmasking important, yet unrecognized, biological difference in B-CLL patients.

Central nervous system involvement in adult acute lymphocytic leukemia.

With effective CNS prophylaxis, most adults with ALL may remain free of CNS leukemia. Several combinations of IT chemotherapy, high-dose systemic chemotherapy, and cranial irradiation have been used with varying results. Excellent prophylaxis can be achieved without cranial irradiation, and in view of the potential acute and long-term toxicity of radiation, these methods may be preferable. A prophylactic approach tailored to the risk of CNS leukemia was shown to be valuable in childhood ALL and in at least one adult study. Further studies should focus on defining risk groups for CNS leukemia and designing effective prophylaxis for each group. More research is needed to define the intensity and duration of treatment and the role of cranial irradiation in the treatment of isolated CNS relapses.

Leptomeningeal metastases: rationale for systemic chemotherapy or what is the role of intra-CSF-chemotherapy?

Malignant subarachnoid deposits complicate both primary central nervous system (CNS) tumors and systemic neoplasms. Although the pathophysiology of symptoms and signs can not be separated by the category of primary tumors that seeds the leptomeninges, the approach to therapy is not similar in primary CNS tumors and in systemic neoplasms. Standard therapy for subarachnoid seeding in primary CNS tumors include conventional or high doses of systemic chemotherapy with various combinations of radiotherapy given either to limited fields or to the whole neuroaxis. Direct administration of chemotherapy to the CSF is not being used. In contrast, whenever a systemic tumor seeds the subarachnoid space the standard approach includes intensive intra-CSF chemotherapy, radiotherapy to limited or extended CNS fields and various combinations of systemic chemotherapy. The published experience with the conventional therapy is reviewed and is critically analyzed. Evidence indicating that high dose systemic chemotherapy can replace intra-CSF treatment in some subgroups are also reviewed and the rationale for this approach is specified. Recent experience in which intra-CSF therapy was prospectively eliminated from the treatment protocol of leptomeningeal metastases of solid tumors reveals that the response rate and survival are similar to those obtained by protocols that differed only by the inclusion of intra-CSF chemotherapy. Patients who were treated by radiotherapy alone combined with systemic chemotherapy but without the intra-CSF therapy were spared the high rate of early and delayed complications directly related to intra-CSF therapy. Still, treatment outcome did not differ. Therefore, future research efforts and prospective clinical trials should investigate the best chemotherapeutic schedules and their sequencing with radiotherapy or with more intensive complementary systemic chemotherapy schemes. Newly designed drugs with long circulation time and improved CNS penetration may serve for this purpose.

[Testicular relapse in acute lymphoblastic leukemia. The experience of a pediatrics service]. / Recidiva testicular na leucemia linfoblastica aguda. A experiencia de um servico.

Testicular relapse in Acute Lymphoblastic Leukemia is a problem which has been developing more and more, as the therapeutic protocols of acute lymphoblastic leukemia are improving. Its appearance, specially during chemotherapy, makes the prognosis of the disease poorer. There have been some diagnostic methods, used in the screening of this situation. The use of more aggressive therapeutic protocols can lead to more encouraging results. The authors of the research present seven children with testicular relapse, which represent 17% of the total group of fourty one boys with acute lymphoblastic leukemia, treated at St. o Antonio Pediatric Ward. They analyse the time of onset, the diagnostic approach of the testicular lesion, the therapeutic protocols chosen for each case and the results.

Immunotoxin therapy of leptomeningeal neoplasia.

Malignant tumors of the central nervous system can result from metastatic dissemination of a variety of cancers. Percutaneous intracisternal injection of an anti-idiotype monoclonal antibody (M6) ricin immunotoxin was shown to be moderately effective in prolonging the survival of tumor bearing animals supporting the use of immunotoxins for the treatment of central nervous system neoplasia (Zovickian J and Youle R.J. J. Neurosurg 68: 767, 1988). This report describes a method that significantly improves the survival of immunotoxin treated Strain 2 guinea pigs in a syngeneic animal model of leptomeningeal neoplasia. Strain 2 guinea pigs, implanted with subarachnoid catheters, received three courses of treatment with an (M6)-intract ricin immunotoxin following intracisternal inoculation of L2C leukemia tumor cells. Animals were treated with three to four micrograms of immunotoxin in three divided doses. This was found to be less toxic and more effective than single bolus administration of immunotoxin. These results demonstrate that a permanent indwelling catheter in this animal model facilitates multiple dose delivery of immunotoxin therapy allowing the assessment of various treatment schedules and the achievement of enhanced therapeutic effect. Furthermore, these results support the continued evaluation of immunotoxins for the treatment of central nervous system neoplasia.

High incidence of meningeal leukemia in lymphoid blast crisis of chronic myelogenous leukemia.

Fifteen patients with lymphoid blast crisis of chronic myelogenous leukemia (LyBC-CML) and five patients with acute lymphoblastic leukemia converting to Philadelphia-positive (Ph+) chronic myeloid leukemia (ALL Ph + CML) were followed. Seven of 15 (46.7%) LyBC-CML patients developed meningeal leukemia within a median period of 6 months (range 2-11 months), while there was no medullary relapse. Five of these responded well to triple intrathecal therapy. In the ALL Ph + CML patients, in spite of central nervous system (CNS) prophylaxis with IT MTX and 18 Gy cranial radiation, two of five patients (40%) experienced meningeal leukemia, one isolated and the other with medullary relapse. The data confirm that LyBC-CML patients experience a high incidence of meningeal leukemia. The role of CNS prophylaxis is not very clear, but its use may delay development and reduce morbidity due to CNS disease.