Studies Of Hairy Cell Leukemia Research Articles

A population-based study of hairy cell leukemia over a period of 20 years

There are limited population-based studies of hairy cell leukemia (HCL), a rare chronic lymphoproliferative disorder of B-cells. We conducted a population-based study that included all patients diagnosed with HCL between 1996 and 2016 in Western Normandy. Recorded data focused on medical history, clinical presentation, biological results, treatment modalities in the first line and in relapsed/refractory patients and the occurrence of secondary malignancies. One hundred and twenty-three HCL patients were registered in the database. HCL represented 0.7% of all malignant hematological disorders and 3.0% of all leukemia. The overall age-standardized incidence ratio (SIR) was 0.39/100,000 inhabitants in men and 0.09/100,000 in women, and it remained stable over the 20-year period analyzed. One hundred and seven patients (88%) received first-line treatment, 33 patients (27%) received at least 2 lines of treatment and 14 patients (11%) received more than 2 lines. Cladribine used as first-line treatment induced a high hematological complete response (HCR) rate of 92%. The median overall survival (OS) was over 15 years, with 5-year and 10-year survival rates of 84% and 70.5%. No significant differences in OS were observed between men and women, between the calendar periods studied or between patients who received a single line treatment with IFN-α or PNA. The risk of relapse was higher with IFN-α treatment, requiring subsequent treatments in that patients. The time to next treatment (TTN) tends to be longer for PNAs compared to IFN-α even if difference is not significant. Secondary cancers were observed in 9/123 patients (7.3%) with solid tumors in 8 patients and hematological malignancy in one patient. Our data confirm in real life that single courses of cladribine administered to patients with HCL induce high response rates, the majority of which are HCR. Relapses seem less frequent than with IFN-α and the administration schedule is less restrictive for the patients. The emergence of chemo-immunotherapy and the development of effective new drugs such as recombinant immunotoxins and BRAF targeting will offer new possibilities in the management of HCL patients.

A population‐based study of hairy cell leukemia in Israel

Few population-based data exist on the incidence and prognosis of hairy cell leukemia (HCL). Our objectives were to study the effect of socio-demographic factors on this rare disease and the risk of second malignancies occurring in HCL patients. We measured crude and age-adjusted incidence rates of HCL based on reporting to the Israel Cancer Registry (ICR) 1991-2001. Using Kaplan-Meier and multivariate analysis, we assessed survival by gender, ethnicity and geographic region. We ascertained additional primary tumors reported in this population and calculated standardized incidence ratios (SIRs) for tumors reported after the diagnosis of HCL. The ICR registered 147 cases of HCL among males and 34 in females between 1991 and 2001. Age-adjusted incidence rates were 1.62/10(6)/yr for women and 7.97/10(6)/yr for men, with rates 1.5 times higher in Jewish than in non-Jewish (mainly Arab) men. Mean overall survival also differed by ethnicity. In a multivariate model, increasing age at diagnosis (P < 0.001), as well as Arab origin (P = 0.008) were associated with poorer survival but gender did not significantly affect the survival after controlling for age and ethnicity. Other primary malignancies were reported in 20 (11%) individuals, with a predominance of genito-urinary tumors (65%) among males. Secondary genito-urinary tumors were significantly increased above the expected population rates (SIR 3.23, 95% confidence interval: 1.39-6.36, P = 0.008). In the Israeli population, age and ethnicity were associated with prognosis of HCL. Variations in disease characteristics, stage of disease at diagnosis or differential access to treatment may contribute to these findings. Patients with HCL appear to be at increased risk for genito-urinary malignancies.

Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature

AbstractComparative expressed sequence hybridization (CESH) to chromosomes is a recently introduced technique that identifies chromosomal regions corresponding to a differential gene expression. This technique is analogous to comparative genomic hybridization (CGH) that detects genomic imbalances. We applied CESH for the study of hairy cell leukemia (HCL), a disorder with a largely unknown expression profile. Twelve HCL cases with spleen involvement were investigated by CESH and CGH. While the latter analysis identified only a few nonrecurrent genomic imbalances, CESH showed a consistent expression profile in all HCL cases. In addition, pairing normal spleen with normal lymph node, a “spleen signature” was established by CESH. This signature most likely reflects the expression profile of spleen-specific components, such as the sinusoidal lining cells from the red pulp and the marginal zone B cells from the white pulp. Imprint of the spleen signature was found in the HCL expression profile, suggesting that HCL may originate from a particular B-cell subset present in these splenic components. Besides pairing HCL with normal lymph node and spleen, we identified an “HCL signature” comprising several chromosome regions with altered expression. The most significantly underexpressed regions include 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24; and 13q31 and Xq13.3-q21 were the most significantly overexpressed. These regions possibly harbor genes related to the biology and the pathogenesis of HCL. Their identification warrants further molecular investigations.

How Reliable is Histologic Examination of Bone Marrow Trephine Biopsy Specimens for the Staging of Non-Hodgkin Lymphoma?: A Study of Hairy Cell Leukemia and Mantle Cell Lymphoma Involvement of the Bone Marrow Trephine Specimen by Histologic, Immunohistochemical, and Polymerase Chain Reaction Techniques

Analysis of non-Hodgkin lymphoma (NHL) involvement of bone marrow trephine biopsy specimens by morphologic features and immunohistochemistry is often difficult, and the criteria for involvement are ill defined. We compared the morphologic and immunohistochemical analysis of B-cell NHL involvement with immunoglobulin heavy chain gene (IgH) rearrangement analysis by polymerase chain reaction (PCR) amplification of the complementarity determining region 3 (CDR3) in bone marrow biopsy specimens from patients with mantle cell lymphoma (n = 53) or hairy cell leukemia (n = 71). By combing morphologic features and phenotype, 54 specimens were considered positive, 62 negative, and 8 inconclusive. PCR analysis showed clonal IgH rearrangements in 46 positive and 6 inconclusive specimens. No clonal IgH rearrangements were present in 61 negative specimens. The 1 false-positive and most false-negative PCR results were likely due to sampling error or DNA degradation of the fixed tissues. In most cases, bone marrow involvement by NHL can be identified by histologic and immunohistochemical examination. Furthermore, clonality of the B-cell population can be detected by amplification of the IgH CDR3 on DNA extracted from bone marrow trephine biopsy sections, which can be helpful in cases diagnosed as inconclusive.

Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL

In 1987 the Italian Cooperative Group for the Study of hairy cell leukemia (HCL) started a prospective trial with the following three major aims: 1) to confirm the effectiveness of alpha-IFN as first-line treatment; 2) to assess the usefulness of splenectomy as consolidation treatment in patients achieving a satisfactory partial remission (PR) with alpha-IFN, and 3) to explore whether splenectomy in patients achieving complete remission (CR) with alpha-IFN can reduce the risk of relapse after discontinuation of the drug. One-hundred seventy-seven patients with histologically-confirmed HCL were registered in the HCL88-A trial between December 1987 and January 1992. Inclusion criteria included no previous treatment and age less than 66 years. All patients received total doses of 3 MU of alpha-IFN daily for 12 months except for those who achieved early CR and would stop treatment after 6 or 9 months. Patients could be treated with different alpha-IFNs. At the time of the present analysis, 166 patients (93.8%) were fully evaluable. Treatment of HCL patients with alpha-IFN at the onset of the disease resulted in 28 CR (16.9%), 103 PR (62.0%), and 27 Minor Remissions (MR) (16.3%). Patients treated with different alpha-IFNs achieved similar results: the overall response rate (CR + PR + MR) was 92.7%, 97.2%, and 95.3% for patients treated with r-alpha-2a, r-alpha 2b, and alpha-N1, respectively. The presence of a leukemic phase and a poor performance status were associated with a statistically significant lower response rate. Patients who were randomly assigned and underwent splenectomy after achieving a PR had a better but not significant 4-year progression-free survival than cases randomized for observation (53% vs. 22%, p = 0.116). Overall, 5 patients died after study entry, with an actuarial 5-year survival rate of 96% for the entire group of 166 patients. After a mean follow-up time of 38 months, only one second malignancy has been recorded. Initial therapy with alpha-IFN, regardless of the type of alpha-IFN used, induces satisfactory responses in the majority of patients with HCL, but in most instances discontinuation of treatment results in recurrence of disease. In most cases alpha-IFN improves the performance status of patients and favors a satisfactory bone marrow recovery and thus could still play a role in the initial management of the disease. Although splenectomy following alpha-IFN could prolong the progression free survival, its use should be restricted to selected cases.

Diagnostic Application of Two-Color Flow Cytometry in 161 Cases of Hairy Cell Leukemia

Recent immunophenotypic studies of hairy cell leukemia (HCL) have suggested specific patterns of immunoreactivity that may aid in diagnosis. We studied peripheral blood (PB) from 161 cases of HCL using two-color direct immunofluorescence flow cytometry and an extended panel of antibody combinations. Circulating hairy cells were identified by immunophenotypic features in 92% of the cases and could be detected even when representing < or = 1% of circulating lymphocytes. The 133 cases with > or = 2% detectable hairy cells were analyzed in detail. HCL showed a uniform and unique B-cell phenotype, with each of the following features identified in 99% to 100% of cases: (1) positive staining for B-ly7, coexpressed with CD19; (2) very intense, uniform expression of CD11c, with CD19; (3) moderately intense staining for CD25, with CD19; (4) very intense staining for CD22; (5) moderate to very intense staining for CD20; and (6) moderately intense monoclonal surface Ig. Phenotypic variability existed in expression of CD10 (26%) and CD5 (4%). Based on these features, HCL was easily distinguished from 50 cases of chronic lymphocytic leukemia (CLL). Although CLL exhibited frequent expression of CD11c (74%) and CD25 (68%), the intensity of staining was significantly less than HCL. Furthermore, CLL was uniformly positive for CD5 and showed weak staining for CD20, CD22, and surface Ig. B-ly7 proved to be the most specific marker, reacting with 100% of HCL cases, but absent in all cases of CLL. We conclude that two-color flow cytometry with specific antibody combinations is an efficacious method for characterization and sensitive detection of hairy cells in PB. Application of the phenotypic criteria described should help to increase accuracy in diagnosis of HCL.

Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia

Recent immunophenotypic studies of hairy cell leukemia (HCL) have suggested specific patterns of immunoreactivity that may aid in diagnosis. We studied peripheral blood (PB) from 161 cases of HCL using two-color direct immunofluorescence flow cytometry and an extended panel of antibody combinations. Circulating hairy cells were identified by immunophenotypic features in 92% of the cases and could be detected even when representing &lt; or = 1% of circulating lymphocytes. The 133 cases with &gt; or = 2% detectable hairy cells were analyzed in detail. HCL showed a uniform and unique B-cell phenotype, with each of the following features identified in 99% to 100% of cases: (1) positive staining for B-ly7, coexpressed with CD19; (2) very intense, uniform expression of CD11c, with CD19; (3) moderately intense staining for CD25, with CD19; (4) very intense staining for CD22; (5) moderate to very intense staining for CD20; and (6) moderately intense monoclonal surface Ig. Phenotypic variability existed in expression of CD10 (26%) and CD5 (4%). Based on these features, HCL was easily distinguished from 50 cases of chronic lymphocytic leukemia (CLL). Although CLL exhibited frequent expression of CD11c (74%) and CD25 (68%), the intensity of staining was significantly less than HCL. Furthermore, CLL was uniformly positive for CD5 and showed weak staining for CD20, CD22, and surface Ig. B-ly7 proved to be the most specific marker, reacting with 100% of HCL cases, but absent in all cases of CLL. We conclude that two-color flow cytometry with specific antibody combinations is an efficacious method for characterization and sensitive detection of hairy cells in PB. Application of the phenotypic criteria described should help to increase accuracy in diagnosis of HCL.

Immunoglobulin gene rearrangements in hairy cell leukemia

Studies of hairy cell leukemia have yielded conflicting data about the cell of origin in this disease. To investigate this issue, we have examined the state of immunoglobulin genes in the cells of 11 randomly selected spleens showing histologic involvement with hairy cell leukemia. DNA was extracted from splenic tissue samples and digested with restriction endonucleases. Following agarose gel electrophoresis and transfer to nitrocellulose filters or activated nylon membranes, splenic DNA was hybridized with radiolabeled DNA fragment probes specific for the constant regions of the immunoglobulin heavy chain and kappa and lambda light chain genes. Autoradiograms of the hybridized DNA in each case revealed rearrangements of a heavy chain gene and at least one light chain gene. In addition, immunophenotyping of cellular immunoglobulin polypeptides was carried out on frozen tissue sections from all but one case. In each case in which an immunoglobulin polypeptide could be detected, a rearrangement was present in the DNA of the corresponding immunoglobulin gene. These studies offer strong evidence for endogenous immunoglobulin synthesis in hairy cells and for the B lymphocytic character of this leukemia.

Immunoglobulin Gene Rearrangements in Hairy Cell Leukemia

Studies of hairy cell leukemia have yielded conflicting data about the cell of origin in this disease. To investigate this issue, we have examined the state of immunoglobulin genes in the cells of 11 randomly selected spleens showing histologic involvement with hairy cell leukemia. DNA was extracted from splenic tissue samples and digested with restriction endonucleases. Following agarose gel electrophoresis and transfer to nitrocellulose filters or activated nylon membranes, splenic DNA was hybridized with radiolabeled DNA fragment probes specific for the constant regions of the immunoglobulin heavy chain and kappa and lambda light chain genes. Autoradiograms of the hybridized DNA in each case revealed rearrangements of a heavy chain gene and at least one light chain gene. In addition, immunophenotyping of cellular immunoglobulin polypeptides was carried out on frozen tissue sections from all but one case. In each case in which an immunoglobulin polypeptide could be detected, a rearrangement was present in the DNA of the corresponding immunoglobulin gene. These studies offer strong evidence for endogenous immunoglobulin synthesis in hairy cells and for the B lymphocytic character of this leukemia.

An ultrastructural study of hairy-cell leukemia: Report of one case in a Chinese

Hairy cell leukemia is a rather rare malignant lymphoreticular disorder. In U.S.A. Bouroncle gave a case incidence of approximately 2% of all leukemias. In China only a few cases have been reported according to a monograph entitled 'Leukemia' written in Chinese by a grout) of authors working in the Haematology Laboratory of the First Hospital affiliated to the Medical University of Wuhan. Recently, a case has been discovered in a Chinese in Singapore (Shannugaratnam*) and probably another in Taiwan (Huang*). We report here a case in whom the hairy cells have been studied by scanning and transmission electron microscopies.For TEM, lymphoid cells isolated from peripheral blood by ficoll solution and centrifugation were fixed in 2.5% glutaraldehyde for 1 hour. Routine procedures were followed for dehydration and embedding in Spon 812. The stained sections were examined with a Philips EM 300 at 60 kV. For SSM, the pre-fixed specimens were dehydrated, critically dried, coated with goldpalladium and examined with a Cambridge Stereoscan 150 EM at 20 kV.

Cytogenetic studies of hairy cell leukemia

Mononuclear cells from peripheral blood and spleen of four patients with hairy cell leukemia (HCL) were cultured for 1 to 10 days with and without phytohemagglutinin (PHA) stimulation. Blastogenesis and mitoses were not observed in the unstimulated cells cultured for up to 3 days. Prolonging the culture time of unstimulated cells to 7 days produced blastogenic response; a further increase in culture time to 10 days showed transformed cells but not mitoses. Poor PHA response was noted in the cultures stimulated for 3 days, but cells cultured for 7 days and then stimulated with PHA entered mitosis. Surface immunoglobulins were exhibited in 78–94% of the cells in the blood and spleen of patients. In addition, these cells had tartarate-resistant acid phosphatase and were able to phagocytize latex particles by which properties they were identified as hairy cell leukemia cells. Chromosome abnormalities were present in a proportion of cells of each patient, none of them, however, were clonal.