scholarly journals Progress report on chlorambucil therapy in postsplenectomy patients with progressive hairy cell leukemia

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 464-467 ◽  
Author(s):  
HM Golomb
Keyword(s):  
Bone Marrow ◽  
Hairy Cell Leukemia ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Hairy Cells ◽  
Total Bone Marrow ◽  
Single Agent Chemotherapy

Abstract Of eight patients with progressive hairy cell leukemia who were treated with daily doses of an alkylating agent (chlorambucil, 4 mg) for at least 6 mo, seven have had an objective response, as measured by improved blood counts. Two patients were pancytopenic and had almost total bone marrow replacement with hairy cells at the initiation of chemotherapy; approximatley 6 mo later, their blood counts and bone marrow had improved dramatically. The five other patients had the leukemic form of the disease, and all responded to therapy. It is important to identify postsplenectomy patients with progressive disease in order to initiate low-dose single-agent chemotherapy.

scholarly journals Progress report on chlorambucil therapy in postsplenectomy patients with progressive hairy cell leukemia

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 464-467
Author(s):  
HM Golomb
Keyword(s):  
Bone Marrow ◽  
Hairy Cell Leukemia ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Hairy Cells ◽  
Total Bone Marrow ◽  
Single Agent Chemotherapy

Of eight patients with progressive hairy cell leukemia who were treated with daily doses of an alkylating agent (chlorambucil, 4 mg) for at least 6 mo, seven have had an objective response, as measured by improved blood counts. Two patients were pancytopenic and had almost total bone marrow replacement with hairy cells at the initiation of chemotherapy; approximatley 6 mo later, their blood counts and bone marrow had improved dramatically. The five other patients had the leukemic form of the disease, and all responded to therapy. It is important to identify postsplenectomy patients with progressive disease in order to initiate low-dose single-agent chemotherapy.

scholarly journals Treatment of hairy cell leukemia (leukemic reticuloendotheliosis) II. Chlorambucil therapy in postsplenectomy patients with progressive disease

Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 305-309
Author(s):  
HM Golomb ◽  
U Mintz
Keyword(s):  
Hairy Cell Leukemia ◽  
Alkylating Agent ◽  
Low Dose ◽  
Progressive Disease ◽  
Bone Marrow Involvement ◽  
Single Agent ◽  
Objective Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Single Agent Chemotherapy

Four postsplenectomy patients with progressive hairy cell leukemia were treated with daily low doses of an alkylating agent (chlorambucil, 4 mg). An objective response, measured by improvement in blood counts in four patients as well as decreased bone marrow involvement on core biopsy in three patients, could be documented within 6 mo. It is important to identify the postsplenectomy patient with progressive disease as early as possible in order to initiate low-dose single agent chemotherapy and have the time necessary to effect an objective response.

scholarly journals Treatment of hairy cell leukemia (leukemic reticuloendotheliosis) II. Chlorambucil therapy in postsplenectomy patients with progressive disease

Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 305-309 ◽  
Author(s):  
HM Golomb ◽  
U Mintz
Keyword(s):  
Hairy Cell Leukemia ◽  
Alkylating Agent ◽  
Low Dose ◽  
Progressive Disease ◽  
Bone Marrow Involvement ◽  
Single Agent ◽  
Objective Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Single Agent Chemotherapy

Abstract Four postsplenectomy patients with progressive hairy cell leukemia were treated with daily low doses of an alkylating agent (chlorambucil, 4 mg). An objective response, measured by improvement in blood counts in four patients as well as decreased bone marrow involvement on core biopsy in three patients, could be documented within 6 mo. It is important to identify the postsplenectomy patient with progressive disease as early as possible in order to initiate low-dose single agent chemotherapy and have the time necessary to effect an objective response.

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.

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).

Continued Response off Treatment After BRAF Inhibition in Refractory Hairy Cell Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4600-4600
Author(s):  
Sascha Dietrich ◽  
Jennifer Hüllein ◽  
Michael Hundemer ◽  
Nicola Lehners ◽  
Alexander Jethwa ◽  
...  
Keyword(s):  
Disease Control ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Drug Exposure ◽  
Objective Response ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Recurrent Mutations ◽  
Hairy Cells

Abstract Abstract 4600 Targeted intervention against driver mutations is beginning to transform cancer treatment. A particular activating mutation of the BRAF serine/threonine protein kinase, BRAF V600E, is found in virtually all cases of hairy-cell leukemia (HCL), suggesting disease-specific oncogene dependence. Here, we present the extended follow up of a patient with chemotherapy refractory HCL who was treated with a short course of vemurafenib, a specific BRAF inhibitor. Before vemurafenib treatment, the patient had an almost complete bone marrow (BM) infiltration by hairy cells and massive splenomegaly (24.8×8.3 cm) leading to severe cytopenias (leukocytes, 680/μl; hemoglobin, 10 g/dl; platelets, 36,000/μl). No objective response could be achieved by three lines of purine analogue based treatment regimens (Cladribine, Pentostatin and R-Cladribine). We demonstrated the presence of the BRAFV600E mutation with a mutation specific antibody and 454 sequencing. In order to investigate if recurrent mutations may have contributed to refractoriness to purine analogues, a panel of genes commonly mutated across lymphoid malignancies were analysed (EZH2, KRAS, MYD88, NOTCH1, NRAS, PIK3CA, SF3B1, or TP53). No mutations were demonstrated Because of limited treatment options and recent success with vemurafenib in BRAF mutated melanoma we decided to use experimental treatment with vemurafenib after intensive counseling and started treatment with 240 mg twice daily after a single loading dose of 960 mg. The dose was slowly escalated to 1,920 mg/d which is the standard dose used in melanoma. After 6 and 16 days of 240mg bid the spleen size had shrunk to 18.8 × 5.8 and 14×5 cm, respectively. Blood counts rapidly recovered and sCD25 which is considered a reliable marker of HCL cell load dropped quickly to normal levels already at the lowest dose of 240 mg vemurafenib bid (Figure 1). There was no evidence of tumor lysis. Response was further evaluated by repeated trephine biopsies on days -1, 6, 17 and 36. After only 6 days of vemurafenib treatment p-ERK signaling was almost completely abolished in HCL cells in vivo, followed by apoptosis of HCL cells as shown by Tunnel staining and finally complete clearance of hairy cells on day 36. CR criteria were achieved on day 43. Because of the excellent disease control and the risk of short-latency non-melanoma skin cancers during therapy with vemurafenib, we discontinued vemurafenib after 56 days. CR continues to persist in the absence of drug exposure for more than 6 months at the time of abstract preparation (Figure 1). Massively parallel DNA sequencing was used to detect remaining mutant BRAF alleles in peripheral blood leukocytes on day 36. Among over 105 sequencing reads, the BRAF V600E mutation was not detectable above background (<0.3% of variant reads). Minimal residual disease (MRD by FACS) assessment of the peripheral blood revealed an approximately 100-fold reduction of hairy cells by day 22 of treatment and a complete eradication from day 36, which continues to persist for more than 6 months. Our observations show that targeting of a single mutated oncogene can provide durable disease control in this leukemia. Trials exploring chemotherapy-free treatment approaches with BRAF inhibitors in HCL are highly warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Morphologic confounders and CD19 negativity in a case of hairy cell leukemia.

2017 ◽  
Vol 9 (1) ◽  
pp. e2017033
Author(s):  
Pulkit Rastogi ◽  
Sreejesh Sreedharanunni ◽  
Uday Yanamandra ◽  
Man Updesh Singh Sachdeva ◽  
Neelam Varma
Keyword(s):  
Bone Marrow ◽  
Hairy Cell Leukemia ◽  
Plasma Cell Dyscrasia ◽  
Molecular Testing ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cell Hyperplasia ◽  
Reactive Plasmacytosis ◽  
Cd10 Expression ◽  
Hairy Cells

Objectives:We report a case of hairy cell leukemia (HCL) initially misdiagnosed as plasma cell dyscrasia due to various clinical, morphological and immunophenotypic confounders.Methods and results:In a patient diagnosed of marrow plasmacytosis and serum monoclonal protein elsewhere and referred to our hospital, morphological evaluation of bone marrow aspirate smears and trephine biopsy, immunophenotyping, and molecular testing (BRAFV600E mutation) were done. Clinically, the patient was asymptomatic, bone marrow revealed plasmacytosis, mastocytosis and lymphocytosis with a few “hairy” cells. Immunophenotyping revealed features of HCL with aberrant CD10 expression and a subclone of CD19neg cells. A diagnosis of HCL with reactive plasmacytosis and mast cell hyperplasia was made and confirmed by immunophenotyping and molecular studies.Conclusion:Hematopathologists must be aware of various confounding factors and should judiciously use flow cytometric and molecular studies for attaining a proper diagnosis of HCL. We also report a very rare immunophenotypic aberrancy (CD 19 negativity) in HCL

scholarly journals Flow cytometry of blood and bone marrow cells from patients with hairy cell leukemia: phenotype of hairy cells and lymphocyte subsets after treatment with 2-chlorodeoxyadenosine

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3672-3681 ◽  
Author(s):  
G Juliusson ◽  
R Lenkei ◽  
J Liliemark
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Nk Cells ◽  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cd4 Cells ◽  
Normal Range ◽  
Hla Dr ◽  
Hairy Cells

Abstract By flow cytometry and an extensive set of markers, we characterized leukemic cells from the blood and bone marrow of 68 symptomatic patients with hairy cell leukemia (HCL). Hairy cells identified in the large cell gate always expressed CD19, CD20, HLA-DR, CD45RA, and B-ly 7. Other markers were occasionally expressed, such as CD38, CD45RO, CD23, CD15, CD4, CD5, and CD10 (expressed on more than 20% of the hairy cells in 44%, 25%, 21%, 18%, 12%, 10%, and 5% of evaluated cases, respectively). During treatment with 2-chlorodeoxyadenosine (CdA), the median lymphocyte counts decreased from 2,000/microL to 300/microL. Flow cytometry was repeated at the nadir (n = 24) of lymphocyte counts, at 3 months (n = 46), at 6 months (n = 50), at 1 year (n = 39), and at 2 years (n = 12) after treatment. The initial decrease of CD8+ and CD20+ cells was greater than that of CD4+ and natural killer (NK) cells, leading to an increasing CD4/CD8 ratio. Median nadir values of CD4+, CD8+, CD20+, and NK cells were 128/microL, 78/microL, 10/microL, and 13/microL, respectively. The subsequent recovery was quicker for CD8+ and NK cells, leading to a normalization within 3 months, whereas CD20+ and CD4+ cells required 1 or 2 years to enter the normal range. The CD4/CD8 ratio thus decreased after the nadir and remained less than 1. CD45RA+ CD4 cells and CD45RA+/CD45RO+ double-positive cells were less affected by CdA. Activated T cells, ie, HLA-DR+ cells, rarely decreased below the normal range and often recovered with an overshoot. CD10+ cells increased in the bone marrow posttreatment as an indication of normal B-cell regeneration in 16 of 36 (44%) patients. The quick regeneration of certain lymphoid subsets might explain the lack of late infections in CdA-treated HCL patients.

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