Decrease of Bone Marrow Fibrosis in Hairy Cell Leukemia (HCL) after 2-CdA Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4574-4574
Author(s):  
Pavel Zak ◽  
Karel Dedic
Keyword(s):  
Bone Marrow ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Fibrosis ◽  
Reticulin Fibers ◽  
Reticular Fibers ◽  
Before And After ◽  
Grade Ii ◽  
Hairy Cells ◽  
Marrow Fibrosis

Abstract Different degree of bone marrow fibrosis is commonly described in patients with HCL. Hairy cells produce and assemble an insoluble matrix of fibronectin, which is responsible for the bone marrow fibrosis. Production of fibronectin is related to activity of the disease. The aim of our study was to evaluate the change of bone marrow fibrosis before and after 2-CdA therapy. Patients and methods: 18 patients, who were treated with 2-CdA and achieved complete remission in 6 months, were included in this analyses. Trephin bone marrow biopsy were obtained before therapy and after therapy in 12 and 24 moths. The 3μm thick section were stained with Gomori reticulin stain. Grading of reticulin fibrosis (scale of 0 to IV): grade 0 - reticulin fibers (RF) absent, grade I - scattered RF or foci of fine reticular network (RN), grade II - diffuse fine RN, grade III - diffuse fine RN and scattered thick fibers, grade IV - diffuse thick reticular fibers and presence of collagen fibers. Results: Before 2-CdA therapy: reticulin fibrosis was grade 0 in 0 p., I in 3p., II in 4p, III in 11p., IV in 0p.. Decrease of reticulin fibrosis in 12 months after 2-CdA was demonstrated in 51% of patients (grade 0 in 1, I in 8p., II in 5p., III in 4p., IV in 0p.), in 24 moths 77% of patients (grade 0 in 2, I in 10p., II in 4p., III in 2p., IV in 0p). Bone marrow fibrosis was increased by one grade in 3p. in 24 months after therapy. Conclusion: Successful 2-CdA therapy in patient with 2-CdA leads to significant reduction of bone marrow fibrosis.

scholarly journals The bone marrow fibrosis of hairy-cell leukemia is caused by the synthesis and assembly of a fibronectin matrix by the hairy cells

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 497-504 ◽  
Author(s):  
J Burthem ◽  
JC Cawley
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Fibrosis ◽  
Amino Terminal ◽  
Hairy Cells ◽  
Marrow Fibrosis

Hairy-cell leukemia (HCL) is a proliferation of clonal B-lymphocytes with features of activation. The disease has a number of distinctive characteristics, prominent among which is the fine reticulin fibrosis invariably present in the bone marrow. However, fibroblast infiltration has never been noted in the marrow and the origin of the fibrosis has not been established. The present studies show that the hairy cells (HCs) of HCL produce an insoluble matrix of fibronectin (FN) in vitro. FN synthesis was shown by the appearance of cellular FN on the surface of cells cultured in serum-free medium and by immunoprecipitation of the metabolically labeled protein from HC aggregates. Moreover, the HCs were shown to assemble FN into disulphide-bonded multimers. This assembly was blocked by a 70-kD amino-terminal fragment of the molecule that blocks FN multimer formation by fibroblasts. HCs expressed abundant VLA-5, an FN receptor not present on normal circulating B lymphocytes, but important in matrix formation. Furthermore, HCs were shown to adhere to an FN fragment containing the VLA-5 binding site. It is therefore suggested that the VLA-5 of HCs is implicated in their assembly of FN matrix. The in vivo relevance of the findings was established by the demonstration of FN in association with infiltrating HCs in bone marrow sections from patients with HCL. It is concluded that the HCs synthesise and assemble an FN matrix and that this is at least partly responsible for the bone marrow fibrosis so characteristic of the disease.

scholarly journals The bone marrow fibrosis of hairy-cell leukemia is caused by the synthesis and assembly of a fibronectin matrix by the hairy cells

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 497-504 ◽  
Author(s):  
J Burthem ◽  
JC Cawley
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Fibrosis ◽  
Amino Terminal ◽  
Hairy Cells ◽  
Marrow Fibrosis

Abstract Hairy-cell leukemia (HCL) is a proliferation of clonal B-lymphocytes with features of activation. The disease has a number of distinctive characteristics, prominent among which is the fine reticulin fibrosis invariably present in the bone marrow. However, fibroblast infiltration has never been noted in the marrow and the origin of the fibrosis has not been established. The present studies show that the hairy cells (HCs) of HCL produce an insoluble matrix of fibronectin (FN) in vitro. FN synthesis was shown by the appearance of cellular FN on the surface of cells cultured in serum-free medium and by immunoprecipitation of the metabolically labeled protein from HC aggregates. Moreover, the HCs were shown to assemble FN into disulphide-bonded multimers. This assembly was blocked by a 70-kD amino-terminal fragment of the molecule that blocks FN multimer formation by fibroblasts. HCs expressed abundant VLA-5, an FN receptor not present on normal circulating B lymphocytes, but important in matrix formation. Furthermore, HCs were shown to adhere to an FN fragment containing the VLA-5 binding site. It is therefore suggested that the VLA-5 of HCs is implicated in their assembly of FN matrix. The in vivo relevance of the findings was established by the demonstration of FN in association with infiltrating HCs in bone marrow sections from patients with HCL. It is concluded that the HCs synthesise and assemble an FN matrix and that this is at least partly responsible for the bone marrow fibrosis so characteristic of the disease.

scholarly journals Effect of alpha-interferon therapy on bone marrow fibrosis in hairy cell leukemia

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 936-939
Author(s):  
M Laughlin ◽  
A Islam ◽  
M Barcos ◽  
P Meade ◽  
H Ozer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Population ◽  
Hairy Cell Leukemia ◽  
Collagen Content ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Fibrosis ◽  
Ifn Therapy ◽  
Hairy Cells ◽  
Marrow Fibrosis

Abstract Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month intervals during, and in six patients 6 months after cessation of therapy. All patients presented with increased bone marrow fibrosis ranging from focally increased reticulin to a diffuse increase in both reticulin and collagen content. This fibrosis was observed to decrease during alpha- IFN therapy inasmuch as the hairy cell population was diminished in the bone marrow in 13 patients. Regression analysis of HCl v bone marrow fibrosis showed a positive correlation (r = .73, P less than .02). Six patients demonstrated a reduction in bone marrow reticulin and collagen to normal levels during alpha-IFN therapy. Two of six patients demonstrated increased bone marrow fibrosis and HCl 6 months after cessation of alpha-IFN therapy. Three of 16 patients exhibited no decrease in bone marrow reticulin content during therapy despite a decreased bone marrow hairy cell population.

scholarly journals Effect of alpha-interferon therapy on bone marrow fibrosis in hairy cell leukemia

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 936-939 ◽  
Author(s):  
M Laughlin ◽  
A Islam ◽  
M Barcos ◽  
P Meade ◽  
H Ozer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Population ◽  
Hairy Cell Leukemia ◽  
Collagen Content ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Fibrosis ◽  
Ifn Therapy ◽  
Hairy Cells ◽  
Marrow Fibrosis

Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month intervals during, and in six patients 6 months after cessation of therapy. All patients presented with increased bone marrow fibrosis ranging from focally increased reticulin to a diffuse increase in both reticulin and collagen content. This fibrosis was observed to decrease during alpha- IFN therapy inasmuch as the hairy cell population was diminished in the bone marrow in 13 patients. Regression analysis of HCl v bone marrow fibrosis showed a positive correlation (r = .73, P less than .02). Six patients demonstrated a reduction in bone marrow reticulin and collagen to normal levels during alpha-IFN therapy. Two of six patients demonstrated increased bone marrow fibrosis and HCl 6 months after cessation of alpha-IFN therapy. Three of 16 patients exhibited no decrease in bone marrow reticulin content during therapy despite a decreased bone marrow hairy cell population.

scholarly journals Bone marrow fibrosis (pseudo-myelofibrosis) in human kala-azar

2000 ◽  
Vol 33 (4) ◽  
pp. 363-366 ◽  
Author(s):  
Francisco Dário Rocha Filho ◽  
Francisco Valdeci de Almeida Ferreira ◽  
Flávia de Oliveira Mendes ◽  
Fernanda Nogueira Holanda Ferreira ◽  
Alexandre Karbage ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iliac Crest ◽  
Histological Analysis ◽  
Blood Parameters ◽  
Bone Marrow Fibrosis ◽  
Iliac Crest Biopsy ◽  
The Third ◽  
Kala Azar ◽  
Reticulin Fibers ◽  
Marrow Fibrosis

Thirty cases of human kala-azar were diagnosed by iliac crest biopsy and myeloculture. Histological analysis of 12 patients showed diffuse thickening of reticulin fibers. To the best of our knowledge, this is the third report describing secondary bone marrow fibrosis (myelofibrosis-like) associated with kala-azar. Patients with positive bone marrow fibrosis (pbmf = 12) were compared to patients without detectable bone marrow fibrosis (wbmf = 18). There were no significant differences in clinical and blood parameters following treatment. All patients showed regression of hepatosplenomegaly.Our findings suggest that associated bone marrow fibrosis is transient and did not interfere in the evolution of treated patients.

scholarly journals Low-dose deoxycoformycin in the treatment of hairy cell leukemia

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1119-1122 ◽  
Author(s):  
EH Kraut ◽  
BA Bouroncle ◽  
MR Grever
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Hairy Cell Leukemia ◽  
Low Dose ◽  
Intravenous Bolus ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Normal Peripheral Blood ◽  
Hairy Cells ◽  
Reversible Reduction

Abstract Ten patients with progressive hairy cell leukemia were treated with 2′deoxycoformycin (dCF) by intravenous bolus (4 mg/m2) given every other week. All ten patients are evaluable for response and nine of the ten patients have achieved a complete remission. In addition to clearing of hairy cells from the bone marrow, eight patients had resolution of their monocytopenia. Seven of the nine patients remain in unmaintained remission with a median duration of 6.2 months. Two patients have had relapse in the bone marrow alone and continue to have normal peripheral blood counts. They are being followed without treatment. Toxicity was minimal at this low dose with one patient having a mild reversible reduction in creatinine clearance. Four other patients had reversible neutropenia. There were no significant infections associated with treatment. Low-dose deoxycoformycin administered intravenously every other week represents an extremely effective treatment for hairy cell leukemia.

Treatment of hairy cell leukemia with alternating cycles of pentostatin and recombinant leukocyte A interferon: results of a phase II study.

1990 ◽  
Vol 8 (4) ◽  
pp. 721-730 ◽  
Author(s):  
A Martin ◽  
S Nerenstone ◽  
W J Urba ◽  
D L Longo ◽  
J B Lawrence ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hairy Cell Leukemia ◽  
Pathologic Complete Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cell Infiltrate ◽  
Recombinant Interferon ◽  
Bone Marrow Biopsies ◽  
Hairy Cells

Fifteen patients with hairy cell leukemia (HCL) were treated with deoxycoformycin (pentostatin; dCF) (4 mg/m2 intravenous [IV] every week x 3) and recombinant interferon-alpha 2a (rIFN-alpha 2a) (3 x 10(6) units subcutaneously [SC] daily x 4 weeks) in alternating months for a total of 14 months. Eleven patients had undergone splenectomy; four had received prior systemic therapy with chlorambucil and/or steroids. All 15 are evaluable for toxicity and peripheral blood response, while 14 are assessable for bone marrow response. Toxicity was tolerable with grade 3 or 4 nausea and vomiting in three patients, neutropenic fevers in five, transient but significant depression in eight, and localized cutaneous herpes zoster in four. Circulating hairy cells were undetectable by the end of the first month in 10 of 13 patients, and by the end of the second month in the other three. Fourteen patients had bilateral bone marrow biopsies performed at baseline after 6 months of treatment, at the end of treatment (14 months), and at 6-month intervals during follow-up. Before treatment, all patients had hypercellular marrows with hairy cels replacing normal marrow elements; all showed at least a 95% clearing of their hairy cell infiltrate by 6 months of therapy. However, small collections of residual hairy cells could be detected intermittently on at least one side of bilateral samples in all patients. All patients have completed treatment with a median duration of follow-up off therapy of 27 months (range, 15 to 31 months). To date, all peripheral counts and serum soluble interleukin-2 receptor (sIL2R) levels remain stable, and no patient has had progression of the hairy cell infiltrate in the bone marrow. Although no patient achieved a pathologic complete response, alternating monthly cycles of dCF and rIFN-alpha 2a produced durable partial remissions (PRs) in all patients. Continued follow-up is required to determine the length of such remissions.

Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia

2016 ◽  
Vol 69 (9) ◽  
pp. 810-816 ◽  
Author(s):  
Eda Tanrikulu Simsek ◽  
Ahmet Emre Eskazan ◽  
Mahir Cengiz ◽  
Muhlis Cem Ar ◽  
Seda Ekizoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Imatinib Therapy ◽  
Imatinib Treatment ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Significant Difference ◽  
Grade Ii ◽  
Marrow Fibrosis

AimsBefore the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy.MethodsThe study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated.ResultsSevere MF (grade II–III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0–I) and severe (grade II–III) groups (p=0.278).ConclusionsAccording to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.

Hairy-cell leukemia: induction of complete remission with pentostatin (2'-deoxycoformycin).

1984 ◽  
Vol 2 (12) ◽  
pp. 1336-1342 ◽  
Author(s):  
A S Spiers ◽  
S J Parekh ◽  
M B Bishop
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Hairy Cell Leukemia ◽  
Bone Marrow Aspiration ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Highly Active ◽  
Extensive Evaluation ◽  
Ann Arbor ◽  
Hairy Cells

Two men with advanced but previously untreated B cell hairy-cell leukemia were treated with low doses of pentostatin (2'-deoxycoformycin) in intermittent courses. There was prompt clearance of hairy cells from the blood, regression of splenomegaly and lymphadenopathy, and correction of anemia, thrombocytopenia, and granulocytopenia. Side effects were tolerable and myelosuppression was not observed. Both patients achieved complete remission documented by bone marrow aspiration and biopsy and radionuclide scans of liver and spleen. They remain in complete remission nine and six months, respectively, after their last treatment. Pentostatin (Warner-Lambert, Ann Arbor, Mich) is highly active in hairy-cell leukemia and merits more extensive evaluation in this disease. A woman with hairy-cell leukemia has begun treatment with pentostatin, and at ten weeks there is disappearance of gross splenomegaly and clearance of hairy cells from the blood. Bone marrow studies have not yet been repeated.

scholarly journals Treatment of hairy cell leukemia with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 817-820 ◽  
Author(s):  
G Flandrin ◽  
F Sigaux ◽  
S Castaigne ◽  
C Billard ◽  
M Aguet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hairy Cell Leukemia ◽  
Alpha Interferon ◽  
Initial Increase ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies ◽  
Biopsy Specimens ◽  
Hairy Cells ◽  
Normal Controls

Abstract Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 patients. Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of thrombocytopenia often appeared within 2 months and usually preceded improvement of anemia, monocytopenia, and neutropenia. Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 patients by the fourth month and in 3 of 8 additional patients by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

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