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2.
Oncologist ; 24(9): 1237-1245, 2019 09.
Article in English | MEDLINE | ID: mdl-30842245

ABSTRACT

Leptomeningeal disease is a rare complication of chronic lymphocytic leukemia (CLL). We report a case of leptomeningeal disease in CLL with a complete clinical response and clearance of cerebral spinal fluid (CSF) after treatment with ibrutinib and intrathecal rituximab. In a comprehensive review of the published literature since 1976, we found 136 cases of CLL with leptomeningeal spread. We found that leptomeningeal disease in patients with CLL responds favorably to treatment in most cases and is associated with longer overall survival than is expected for other cancers. Clearance of CSF is associated with improved survival. Treatment with rituximab and ibrutinib is more frequently associated with complete response compared with older agents. IMPLICATIONS FOR PRACTICE: The incidence of leptomeningeal CLL is more common than previously described and can be recognized by attention to certain symptoms and signs. This case presentation and literature review reveals that, in many cases, leptomeningeal lymphomatosis is reversible with the use of rituximab and ibrutinib. The authors show a survival benefit associated with treating to cerebral spinal fluid (CSF) clearance by cytology and compare outcomes with various treatment strategies, focusing on novel agents. Now that there is effective therapy for leptomeningeal lymphoma in CLL, the importance for oncologists to recognize this neurologic complication has become clear.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Meningeal Carcinomatosis/drug therapy , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage , Rituximab/administration & dosage , Adenine/analogs & derivatives , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Male , Meningeal Carcinomatosis/cerebrospinal fluid , Meningeal Carcinomatosis/complications , Meningeal Carcinomatosis/diagnosis , Middle Aged , Piperidines , Remission Induction
5.
Haematologica ; 101(4): 458-65, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26819053

ABSTRACT

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic leukemia are due to other etiologies in approximately 80% of cases. Analysis of the cerebrospinal fluid has high sensitivity but limited specificity to distinguish clinically significant chronic lymphocytic leukemia involvement from other etiologies.


Subject(s)
Biomarkers, Tumor/cerebrospinal fluid , Central Nervous System Neoplasms/diagnosis , Central Nervous System/metabolism , Hermanski-Pudlak Syndrome/diagnosis , Immunologic Deficiency Syndromes/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , ADP-ribosyl Cyclase 1/cerebrospinal fluid , ADP-ribosyl Cyclase 1/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Cell Count , Central Nervous System/pathology , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/mortality , Diagnosis, Differential , Female , Flow Cytometry , Hermanski-Pudlak Syndrome/cerebrospinal fluid , Hermanski-Pudlak Syndrome/genetics , Hermanski-Pudlak Syndrome/mortality , Humans , Immunoglobulin Heavy Chains/cerebrospinal fluid , Immunoglobulin Heavy Chains/genetics , Immunologic Deficiency Syndromes/cerebrospinal fluid , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/mortality , Integrin alpha4/cerebrospinal fluid , Integrin alpha4/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Magnetic Resonance Imaging , Male , Middle Aged , Primary Immunodeficiency Diseases , Retrospective Studies , Spinal Puncture , Survival Analysis , ZAP-70 Protein-Tyrosine Kinase/cerebrospinal fluid , ZAP-70 Protein-Tyrosine Kinase/genetics
6.
Int J Hematol ; 85(4): 323-5, 2007 May.
Article in English | MEDLINE | ID: mdl-17483076

ABSTRACT

Leukemic involvement of the central nervous system (CNS) in previously undiagnosed chronic lymphocytic leukemia (CLL) is very rare. We report the case of a 62-year-old man with neuroborreliosis in which cytologic, immunocytochemical, and flow cytometry analyses revealed the presence of clonal B-lymphocytes in the cerebrospinal fluid (CSF). After the patient received antimicrobial therapy, his meningeal symptoms cleared up, and the number of cells in the CSF decreased. Monoclonal lymphocytes were still detectable at the same percentage, however, despite systemic chlorambucil therapy. The application of intrathecal dexamethasone therapy led to the disappearance of B-cell CLL (B-CLL) cells in the CSF. We presumed that the neuroborreliosis enabled the transmigration of leukocytes, including B-CLL cells, across the blood-brain barrier via activation of matrix metalloproteinase 9, an enzyme known to open the blood-brain barrier.


Subject(s)
Central Nervous System/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Leukemic Infiltration/drug therapy , Leukemic Infiltration/pathology , Lyme Neuroborreliosis/drug therapy , Lyme Neuroborreliosis/pathology , Anti-Infective Agents/administration & dosage , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Hormonal/administration & dosage , Blood-Brain Barrier/enzymology , Blood-Brain Barrier/pathology , Central Nervous System/enzymology , Chlorambucil/administration & dosage , Dexamethasone/administration & dosage , Enzyme Activation/drug effects , Humans , Injections, Spinal , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/enzymology , Leukemic Infiltration/cerebrospinal fluid , Leukemic Infiltration/enzymology , Lyme Neuroborreliosis/cerebrospinal fluid , Lyme Neuroborreliosis/complications , Lyme Neuroborreliosis/enzymology , Male , Matrix Metalloproteinase 9/metabolism , Middle Aged
7.
Clin Lab Haematol ; 28(1): 69-71, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16430465

ABSTRACT

A 75-year-old man, with a long history of recurrent lymphoplasmacytoid lymphoma, presented with diffuse large-cell lymphoma affecting adrenal glands and causing severe hypoadrenalism. The lymphoma responded to rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy. Seven months postcompletion of chemotherapy, he developed signs of gastroenteritis and septicaemia. He deteriorated 24 h postadmission with a significant fall in Glasgow Coma Scale Score. Polymerase chain reaction testing of cerebrospinal fluid suggested enteroviral encephalitis. He responded symptomatically to intravenous immunoglobulins. His immunoglobulin levels were monitored weekly and supplemented to maintain immunoglobulin G level at 10 g/l, but in spite of this, his neurological condition deteriorated and he died after 14 weeks. Rituximab can cause prolonged B-cell deficiency. We speculate that profound immunosuppression induced by rituximab, together with previous chemotherapy, predisposed this patient to fatal enteroviral meningoencephalitis.


Subject(s)
Antibodies, Monoclonal/adverse effects , Enterovirus Infections/etiology , Immunosuppression Therapy/adverse effects , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Meningoencephalitis/etiology , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Enterovirus Infections/cerebrospinal fluid , Enterovirus Infections/drug therapy , Fatal Outcome , Humans , Immunoglobulins, Intravenous/administration & dosage , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/virology , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/drug therapy , Prednisone/administration & dosage , Prednisone/adverse effects , RNA, Viral/cerebrospinal fluid , Rituximab , Vincristine/administration & dosage , Vincristine/adverse effects
8.
Leuk Lymphoma ; 46(4): 619-21, 2005 Apr.
Article in English | MEDLINE | ID: mdl-16019494

ABSTRACT

Leukemic meningitis is a rare manifestation of chronic lymphocytic leukemia (CLL) and typically occurs in advanced stages. We report the case of a 71-year-old male in whom Binet A, Rai 1 stage CLL was diagnosed in June 2002. The stage called for a "watch and wait" strategy. Six months later the patient presented with paraparesis. Magnetic resonance imaging of the lumbar spine revealed no abnormalities. Lumbar puncture disclosed xanthochromic cerebrospinal fluid (CSF) with 1003 cells/microl, 95% atypical lymphocytes. Flow cytometry confirmed typical features of CLL. Intrathecal injections of methotrexate, cytosine arabinoside and corticosteroids did not substantially reduce the CSF cell count and failed to improve the neurological symptoms. Two weeks later the patient developed a pulmonary embolism complicated by fatal secondary pneumonia. Leukemic meningitis is a rare manifestation of CLL, especially in early stages. Selective spinal paraparesis as the first symptom of meningitis in CLL is even rarer and has been reported only once.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/complications , Meningitis/etiology , Paraparesis/etiology , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Fatal Outcome , Follow-Up Studies , Humans , Injections, Spinal , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Meningitis/cerebrospinal fluid , Paraparesis/cerebrospinal fluid , Treatment Failure
9.
Cytometry B Clin Cytom ; 63(1): 23-7, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15624205

ABSTRACT

BACKGROUND: Morphologically malignant lymphocytes in the cerebrospinal fluid (CSF) are highly suggestive of central nervous system involvement by lymphoid malignancy. Although flow cytometry is increasingly used to detect a monoclonal B-cell population in the CSF, the significance of this finding in the absence of morphologically identifiable malignant cells is unknown. METHODS: We reviewed CSF flow cytometric results in 32 patients studied at a single institution over 5 years and identified patients who had monoclonal B-cells in the CSF. Clinical presentation and course were reviewed. RESULTS: Twelve patients had a monoclonal B-cell population in the CSF, but only three had clinical evidence of malignant CNS disease. Of the other nine patients, 4 had nonmalignant neurologic disease and five had a lymphoproliferative disorder: chronic lymphocytic leukemia (n = 4) and mantle cell lymphoma (n = 1). In patients who had chronic lymphocytic leukemia and mantle cell lymphoma, the monoclonal B-cell population was small and had an immunophenotype identical to that of circulating malignant B cells. None of these nine patients developed clinical evidence of malignant CNS involvement during follow-up. CONCLUSION: In patients who have indolent B-cell malignancies, the presence of monoclonal B cells in the CSF may not be diagnostic of clinically significant CNS involvement by a lymphoid malignancy.


Subject(s)
B-Lymphocytes/pathology , Central Nervous System Diseases/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymphocytosis/cerebrospinal fluid , Lymphoma, Mantle-Cell/pathology , Central Nervous System Diseases/cerebrospinal fluid , Central Nervous System Diseases/etiology , Clone Cells , Flow Cytometry/methods , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Lymphoma, Mantle-Cell/cerebrospinal fluid , Lymphoma, Mantle-Cell/complications
10.
Leuk Lymphoma ; 44(7): 1235-7, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12916878

ABSTRACT

We report a rare case of involvement of the central nervous system (CNS) by chronic lymphocytic leukemia (CLL). A 68-year-old man with prolymphocytic variant of B-CLL (CLL/PLL), develops CNS involvement with headache and vomiting. Computed tomography of the head showed no abnormalities. The cerebrospinal fluid (CSF) revealed numerous lymphocytoid cells of prolymphocytic appearance consistent with findings on the peripheral blood smear. Immunophenotypic analysis demonstrated that the leukemic B cells were positive for CD19, CD20, and HLA-DR, but CD5 was difficult to detect. The patient was treated with intrathecal methotrexate, cytarabine, and hydrocortisone and had improvement in symptoms and CSF findings. Although CNS involvement is an unusual manifestation in CLL, one should be aware of the possibility of this complication in cases presenting with neurological symptoms.


Subject(s)
Cell Transformation, Neoplastic/pathology , Central Nervous System Neoplasms/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Leukemia, Prolymphocytic/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/drug therapy , Humans , Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Prolymphocytic/cerebrospinal fluid , Leukemia, Prolymphocytic/drug therapy , Male
11.
Ann Hematol ; 81(4): 187-91, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11976819

ABSTRACT

Soluble CD27 (sCD27) reportedly is a sensitive and specific marker for leptomeningeal involvement (LI) of CD27-expressing lymphoproliferations such as B-cell non-Hodgkin's lymphoma (B-NHL) or chronic B-lymphocytic leukemia (B-CLL). Because morphological analysis of cerebrospinal fluid (CSF) in patients suspected of LI is false negative in one-third of patients, a diagnostic marker for LI by B-NHL or B-CLL would be very valuable. sCD27 was determined in the first CSF sample from each of 102 unselected patients submitted for (immuno)morphologic detection of malignant cells. The patients were considered to have LI if either (immuno)morphologic analyses showed tumor cells or if neuroradiological evaluation showed typical abnormalities consistent with LI. Patients were suspected of having LI if CSF samples revealed atypical lymphocytes and/or if clinical symptoms and signs suggestive of LI were present, but clinical follow-up was shorter than 3 months because of deterioration of the patient. LI was considered absent if (immuno)morphologic analyses of CSF samples were negative without evidence for LI during 3 months of clinical follow-up. In patients with chronic lymphoproliferative disorders [mainly B-non-Hodgkin's lymphoma (NHL)], sCD27 concentrations were significantly higher in the CSF samples of 16 patients with confirmed or suspected LI than in those of 46 patients without LI. However, sCD27 was also increased in a variety of other predominantly inflammatory neurological disorders including herpes simplex and zoster infections. The positive predictive value of sCD27 determination for LI was only 54%, but the negative predictive value was 92%. Normal sCD27 concentrations in CSF samples of patients with chronic lymphoproliferation makes LI unlikely, but the determination of CSF sCD27 is not sufficiently specific to serve as a reliable tumor marker.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Lymphoma, B-Cell/diagnosis , Meningeal Neoplasms/diagnosis , Tumor Necrosis Factor Receptor Superfamily, Member 7/cerebrospinal fluid , Biomarkers, Tumor/cerebrospinal fluid , Diagnostic Errors/prevention & control , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Meningeal Neoplasms/cerebrospinal fluid , Predictive Value of Tests , Solubility
12.
Rev Med Interne ; 21(8): 698-700, 2000 Aug.
Article in French | MEDLINE | ID: mdl-10989496

ABSTRACT

INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating disease resulting from an opportunistic infection of the central nervous system by JC papovavirus. It mostly occurs in patients with an underlying immunosuppressive disorder. In the era of acquired immunodeficiency syndrome it is observed with increasing frequency. EXEGESIS: We report the case of a non-HIV-infected patient who presented chronic lymphocytic leukemia with progressive multifocal leukoencephalopathy uncovered by both imaging and the presence of JC virus in the cerebrospinal fluid. CONCLUSION: Due to the lack of specific treatment, the disease is still rapidly progressive and fatal.


Subject(s)
JC Virus/isolation & purification , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukoencephalopathy, Progressive Multifocal/complications , Aged , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukoencephalopathy, Progressive Multifocal/cerebrospinal fluid , Leukoencephalopathy, Progressive Multifocal/diagnosis , Magnetic Resonance Imaging , Male
14.
Cancer Pract ; 6(4): 223-8, 1998.
Article in English | MEDLINE | ID: mdl-9767335

ABSTRACT

PURPOSE: This review and case report address the rare complication of leptomeningeal involvement in patients with chronic lymphocytic leukemia. OVERVIEW: Chronic lymphocytic leukemia is the most common form of leukemia, with more than 200,000 cases reported in the past 20 years. An uncommon complication of the disorder is central nervous system invasion. To date, only 21 cases have been reported, and their presenting symptoms have been heterogeneous and often nonspecific, including headache, cranial nerve abnormalities, confusion, ataxia, nausea, vomiting, and fever. The diagnosis is confirmed by the presence of a clonal population of lymphocytes in the cerebrospinal fluid. Treatment is either intrathecal or intraventricular chemotherapy with adjuvant radiation therapy or radiation alone. Prognosis is improved by prompt and aggressive therapy. In this case report, a 61-year-old man developed severe ataxia, vertigo, and occipital headaches 4 weeks after diagnosis with otherwise asymptomatic chronic lymphocytic leukemia. After treatment with both radiation to the head and neck and intrathecal methotrexate the patient achieved complete symptom resolution. Thus far, no additional systemic cytotoxic chemotherapy has been necessary. CLINICAL IMPLICATIONS: Because central nervous system invasion is uncommon in chronic lymphocytic leukemia, it may go undiagnosed and under-reported. Providers of patients with this disease need to be aware of possible central nervous system invasion when patients present with cranial nerve signs or symptoms and/or nonspecific neurologic manifestations. Early identification and prompt central nervous system-directed chemotherapy can affect morbidity and quality of life positively.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Leukemic Infiltration/pathology , Meninges/pathology , Antimetabolites, Antineoplastic/therapeutic use , Diagnosis, Differential , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Leukemic Infiltration/cerebrospinal fluid , Leukemic Infiltration/therapy , Male , Methotrexate/therapeutic use , Middle Aged , Prognosis , Radiotherapy, Adjuvant
15.
Mod Pathol ; 10(5): 500-3, 1997 May.
Article in English | MEDLINE | ID: mdl-9160317

ABSTRACT

The use of polymerase chain reaction (PCR) for routine detection of clonal immunoglobulin heavy-chain (IgH) gene rearrangements represents an attractive alternative to Southern hybridization analysis not only because PCR protocols are quicker and simpler, but also because of the ability to analyze very small population of cells in search of minimal residual disease. This can be especially important for the detection of clonal malignant cells in locations other than bone marrow or peripheral blood. We describe a case in which central nervous system involvement, a very rare complication of chronic lymphocytic leukemia, was confirmed by PCR analysis for IgH genes rearrangement of the lymphocytes found in cerebrospinal fluid. The cerebrospinal fluid and the peripheral blood lymphocytes (obtained from archival cytospins stored at the time of diagnosis, 5 years before) presented an identical IgH gene rearrangement, as shown by sequence analysis. Thus, the use of PCR for IgH genes rearrangement can be very useful in the detection of monoclonality in samples with a small number of cells and in the confirmation of the common origin of B cells in different specimens of the same patient.


Subject(s)
Arachnoid/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Lymphocytes/cytology , Polymerase Chain Reaction/methods , Cerebrospinal Fluid/cytology , DNA/isolation & purification , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Male , Middle Aged , Retrospective Studies
16.
Arch Pathol Lab Med ; 121(5): 524-7, 1997 May.
Article in English | MEDLINE | ID: mdl-9167611

ABSTRACT

Central nervous system involvement in chronic lymphocytic leukemia is rare. We describe a patient with early stage chronic lymphocytic leukemia who developed visual loss and transient paresthesias. Lumbar puncture with cytology and flow cytometry documented leukemic meningitis, which responded to standard treatment; including cranial irradiation and intrathecal chemotherapy. We review the literature of all previously reported cases of brain or meningeal involvement by chronic lymphocytic leukemia and suggest that this complication may frequently go unrecognized.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Meningitis, Aseptic/pathology , Adult , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Male , Meningitis, Aseptic/cerebrospinal fluid , Meningitis, Aseptic/complications , Papilledema/etiology , Vision Disorders/etiology
17.
Acta Haematol ; 88(1): 37-40, 1992.
Article in English | MEDLINE | ID: mdl-1414160

ABSTRACT

An unusual complication of chronic lymphocytic leukemia (CLL) is reported. The patient, a 79-year-old man, had a long standing history of CLL, that had been complicated by the development of a Guillain-Barré-like syndrome and a peripheral biclonal gammopathy. The biclonal immunoglobulins identified in the serum were IgM lambda and IgG lambda. The patient's condition progressed and he eventually developed ophthalmologic complications. Cerebrospinal fluid (CSF) obtained during evaluation of his visual dysfunction contained numerous small, mature lymphocytes consistent with the presence of CLL cells in the central nervous system (CNS); immunoperoxidase staining of these cells revealed a monoclonal population. Protein electrophoretic evaluation of the patient's CSF showed a single monoclonal band and immunofixation electrophoresis of the CSF revealed that the immunoglobulin present was IgG lambda. No evidence for the monoclonal IgM paraprotein identified in serum could be appreciated in the CSF by immunofixation. Taken together, these findings strongly implied that there was CNS involvement by the leukemia and this process caused the patient's neurologic symptoms. Furthermore, this study demonstrates that chronic lymphocytic leukemia should also be considered as one of the hematopoietic malignancies associated with monoclonal gammopathies involving the CNS.


Subject(s)
Central Nervous System/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Paraproteinemias/etiology , Aged , Humans , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/cerebrospinal fluid , Immunoglobulin lambda-Chains/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemic Infiltration , Male , Paraproteinemias/cerebrospinal fluid , Paraproteins/cerebrospinal fluid , Polyradiculoneuropathy/cerebrospinal fluid , Polyradiculoneuropathy/etiology
20.
Acta Haematol ; 81(2): 109-11, 1989.
Article in English | MEDLINE | ID: mdl-2496549

ABSTRACT

A patient with the prolymphocytic variant of B cell chronic lymphocytic leukemia (CLL/PL) who developed meningeal leukemic involvement is reported. He had been diagnosed as having CLL/PL 2.5 years earlier, and treated successively with splenectomy, continuous chlorambucil and CHOP chemotherapy. While receiving the latter treatment, the patient developed persistent cephalalgia and vomiting, without signs of neurological focality. A lumbar puncture yielded a cerebrospinal fluid (CSF) showing lymphoid cells of prolymphocytic appearance and the immunological cell markers demonstrated the clonality of these cells. Intrathecal methotrexate and arabinosyl cytosine treatment was administered, this leading to the disappearance of the abnormal cells from the CSF and the resolution of the clinical symptoms.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Leukemia, Prolymphocytic/pathology , Meningeal Neoplasms/pathology , Biomarkers, Tumor/analysis , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/cerebrospinal fluid , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Prolymphocytic/cerebrospinal fluid , Leukemia, Prolymphocytic/metabolism , Male , Meningeal Neoplasms/analysis , Meningeal Neoplasms/cerebrospinal fluid , Middle Aged
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