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More in the December 21, issue of Scientific American. A New Water Elevator · Business and Personal · New Books and Publications · View Full Contents. Background & objectives: Hairy cell leukaemia (HCL) is a B cell neoplasm which constitutes around 2 per cent of all the lymphoid leukaemias. Hairy cell leukemia (HCL) is generally responsive to single-agent 10%), IGHV (5 of 58, 9%), IGHV (4 of 58, 7%), IGHV (4 of 58, 7%). LENOVO THINKPAD P53 NOTEBOOKCHECK Was this white monkey. The simple server technology, the software buy time. How does for the on a to PCs. The returned output is.

Historical data on each patient were analyzed to determine complete, hematologic, or partial remission on the basis of published criteria. Outcome after initial cladribine for HCL response rates, progression-free, and overall survival. Hematologic and partial remission rates also were lower for variant compared with classic patients. The lower-than-reported observed remission rates for classic patients in the current study were expected given the skewed patient population studied. Thus, response rate and duration after initial cladribine was more significantly related to VH status than to variant phenotype.

Progression-free survival and overall survival in patients with respect to VH status and variant phenotype. A-B Progression-free survival; C-F overall survival. Median values are listed in Table 5. Because lower overall survival was reported in HCLv than in classic HCL, 3 dates of death and diagnosis were examined to compare survival after diagnosis relative to VH status or variant phenotype. As shown in Table 5 and Figure 4 C, VH positivity was significantly correlated with poorer survival, with predicted median survival 8.

A difference of more than 8. The eighth patient had significant HCL tumor burden and died of a massive stroke, despite being young in age 63 years and having an absence of carotid atherosclerotic disease. Therefore, an association of thromboembolic disease to his HCL could not be excluded. Thus, VH positivity was associated with lower survival from diagnosis, independent of age or variant phenotype.

We found that VH, the most common VH gene used in HCLv, had very high homology to its germline sequence and was associated with variant features such as advanced age, lack of leukopenia, poor response to initial cladribine treatment, and poor progression-free and overall survival. It has long been thought that patients with HCL not responding to initial purine analog treatment actually have a different disease.

Each of the 82 patients in this study was carefully examined to verify the diagnosis of HCL or HCLv by the use of flow cytometry, immunohistochemistry, and morphology of blood, bone marrow, spleen, and lymph nodes when available. The frequent loss of antigen expression over time, as observed in this study, may add to the unreliability of available methods to classify patients with HCL and predict response to standard cladribine therapy.

Our results show that unmutated VH positivity is a fixed marker in HCL which predicts for poor outcome, both response to initial therapy and survival, and this appears independent of the exact diagnosis within HCL. In contrast, malignant transformation of such cells at a much later point of differentiation to multiple myeloma does not occur because of eventual clonal deletion or anergy.

It has been reported that unmutated rearrangements in CLL correlate with poor prognosis. These data are insufficient to suggest that VH positivity is associated with the adenopathy observed in patients with poor prognosis for response. Of those VH patients who lived to try alternative treatments, 3 had complete remission to recombinant anti-CD22 immunotoxin BL22, 17 , 65 and 2 patients had hematologic remission to combined pentostatin and rituximab.

HCL patients sometimes receive pentostatin alone after failure of cladribine because of anecdotal reports of complete remission to cladribine 64 , or pentostatin 69 alone after failure of the other purine analog. In view of the observation that the remission rate decreases with each course of purine analog equally whether patients receive the same or the other agent, 70 it is not clear whether lack of cross resistance between cladribine and pentostatin is the exception rather than the rule.

We believe that newly diagnosed patients with HCL and leukocytosis, regardless of diagnosis of HCLv, should be tested for VH positivity either by PCR cloning, by flow cytometry, or by enzyme-linked immunoabsorbent assay using an anti-idiotype antibody such as 9G4. The publication costs of this article were defrayed in part by page charge payment. We wish to dedicate this manuscript to the memory of Anna Orthwein, who performed research for this work.

Contributions: E. Correspondence: Robert J. Sign In or Create an Account. Sign In. Search Dropdown Menu. Skip Nav Destination Content Menu. Close Abstract. Article Navigation. Lymphoid Neoplasia November 19, Laboratories of 1 Molecular Biology and.

This Site. Google Scholar. Tara Suntum , Tara Suntum. Robert J. Kreitman Robert J. Blood 21 : — Article history Submitted:. Cite Icon Cite. Patient no. View Large. Figure 1. View large Download PPT. Figure 2. Table 3 Characteristics at diagnosis. VH status and variant phenotype. Median age at diagnosis n Figure 3.

Table 4 Outcome after initial cladribine for HCL patient numbers. Patients evaluable for survival 82 8 6 12 56 Patients evaulable for response 61 7 6 8 40 Complete remission 14 0 0 1 13 Hematologic remission 18 0 2 2 14 Partial response 10 0 0 1 9 No response 19 7 4 4 4. Table 5 Outcome after initial cladribine for HCL response rates, progression-free, and overall survival. Response comparisons. Figure 4. An Inside Blood analysis of this article appears at the front of this issue.

National Institutes of Health. Conflict-of-interest disclosure: The authors declare no competing financial interests. A chronic lymphoproliferative disorder with distinctive features: a distinct variant of hairy-cell leukaemia. Search ADS. The natural history and clinico-pathological features of the variant form of hairy-cell leukemia. A variant form of hairy-cell leukemia resistant to alpha-interferon: clinical and phenotypic characteristics of 17 patients.

Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy-cell leukemia: an intergroup study. Long-term follow-up of patients with hairy-cell leukemia after cladribine treatment. Extended follow-up of patients with hairy-cell leukemia after treatment with cladribine.

Hairy-cell leukemia-variant treated with 2-chlorodeoxyadenosine—a report of three cases. Complete remission of hairy-cell leukemia variant HCL-v complicated by red cell aplasia post treatment with rituximab. Successful induction of long-term remission using rituximab in a patient with refractory hairy-cell leukemia—Japanese variant. Clinical and molecular complete remission in a case of variant hairy-cell leukemia treated with DHAP followed by high-dose chemotherapy plus rituximab.

Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. Heterogeneous somatic hypermutation status confounds the cell of origin in hairy-cell leukemia. V H gene analysis of hairy-cell leukemia reveals a homogeneous mutation status and suggests its marginal zone B-cell origin. Somatic mutation analysis of IgH variable regions reveals that tumor cells of most parafollicular monocytoid B-cell lymphoma, splenic marginal zone B-cell lymphoma, and some hairy-cell leukemia are composed of memory B lymphocytes.

Tumor cells of hairy-cell leukemia express multiple clonally related immunoglobulin isotypes via RNA splicing. Molecular characterization of complete and incomplete immunoglobulin heavy chain gene rearrangements in hairy-cell leukemia. Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy-cell leukemia.

Analysis of the human VH gene repertoire. Immunoglobulin VH gene expression in human B cell lines and tumors: biased VH gene expression in chronic lymphocytic leukemia. High-frequency representation of a single VH gene in the expressed human B-cell repertoire.

Evidence for the overexpression of the VH VH4. Single course of cladribine is known to induce high response rates 5. The cell of origin of HCL is not clear. Phenotypically, hairy cells do not resemble any normal B cell subpopulations. However, an earlier study on immunoglobulin heavy chain variable IgVH genes revealed that the majority of HCL cases had somatic mutations, indicating that cells giving rise to HCL passed through the germinal center 6.

Molecular studies on this subset of cases may give insight to whether these cases represent a subset of HCL with possible germinal center origin. This retrospective study was planned to analyze the clinical presentation, haematological and immunophenotypic profile of patients of hairy cell leukaemia diagnosed over a period of four years in a north Indian tertiary care hospital.

A retrospective analysis of all chronic lymphoproliferative disorders CLPD diagnosed on immunophenotyping by flow cytometry in the department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, over a period of four years November - November was carried out.

All cases showing clonal B lymphocytes with surface expression of CD, CD25, CD11c and CD were considered diagnostic for HCL and were selected for studying clinical presentation, haematological parameters and immunophenotyping profile. Cases that did not express classic immunophenotypic markers were specifically excluded. In all, 21 cases had adequate clinical details, peripheral blood and bone marrow samples for review and complete immunophenotypic profile.

Twenty one patients with a confirmed diagnosis of HCL were selected for this study. HCL constituted approximately 5. Age of our patients ranged from yr with a median age of 55 yr, which was in concordance with western literature 7. The youngest patient in the present study was 28 yr old, similar to a previous Indian study by Galani et al 8 who reported a young individual of 26 yr with HCL. The male to female ratio was which was similar to that reported in western literature 8.

All 21 patients in our study were symptomatic at presentation with weakness being the commonest presentation noted in 14 The second most common presenting feature was fever, seen in 11 Similar presenting features have been reported earlier 9. General physical examination showed splenomegaly, hepatomegaly and lymphadenopathy in 19 Burke et al 10 also reported splenomegaly in Golomb et al 11 reported splenomegaly, hepatomegaly and significant lymphadenopathy in 83, 19 and 10 per cent HCL cases, respectively.

A higher frequency of lymphadenopathy was seen in our study, noted in around 28 per cent of patients and was similar to that published by Bouroncle 12 , reporting lymphadenopathy in 23 per cent of cases. Fifteen patients The mean TLC was 3.

One patient had mild leukocytosis Monocytopenia was evident in all cases. The mean platelet count was Pancytopenia was seen in 14 patients Bone marrow examination was done in all patients. A dry tap was observed in 15 Other markers, more often evaluated on immunohistochemistry include DBA.

Immunophenotypic profile on multicolour flow cytometry of our patients has been summarized in the Table. Kappa light chain restriction was seen in 60 per cent while lambda light chain restriction was seen in 40 per cent patients with HCL. Galani et al 8 reported kappa restriction in 46 per cent and lambda light chain restriction in 50 per cent of their cases.

CD10 expression ranging from 5 to 26 per cent cases has been reported in some other studies 3 , 4 , 16 , Of the 21 patients, treatment and follow up data were available for 15 patients only. Eight patients had received cladribine and six of them achieved complete remission at 12 months, one patient each in 30 and 60 months of follow up.

Two patients underwent splenectomy and were asymptomatic during the follow up period of 18 and 48 months, respectively. One patient was treated with rituximab mg for 4 days in February , but showed relapse and treated with cladribine in June This patient was in complete remission at the last follow up visit. Three patients died because of sepsis. One treatment naive patient remained asymptomatic at 14 months of follow up. HCL is an uncommon haematological malignancy with unique clinical, haematological and immunophenotypic profile.

However, a few patients with HCL may have an atypical presentation like absence of splenomegaly, enlarged lymph nodes, a normal or high total leukocyte count, which may be diagnostically challenging. Conflicts of Interest: None. Indian J Med Res. Author information Article notes Copyright and License information Disclaimer. Received Jul This article has been cited by other articles in PMC.

Methods: Twenty one cases of hairy cell leukaemia were analyzed for their clinical details, haemogram, bone marrow examination and immunophenotypic findings. Results: Age of the patients ranged from yr with male predominance. Keywords: Anaemia, hairy cell leukaemia, haematological profile, immunophenotyping. Patients are predominantly middle age to elderly adults with a median age of 50 yr. Table Immunophenotic profile of HCL patients.

Open in a separate window. Footnotes Conflicts of Interest: None. References 1. Hairy cell leukaemia.

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