scholarly journals Immunomorphologic analysis of bone marrow biopsies after treatment with 2-chlorodeoxyadenosine for hairy cell leukemia

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4310-4315 ◽  
Author(s):  
DJ Ellison ◽  
RW Sharpe ◽  
BA Robbins ◽  
JC Spinosa ◽  
JD Leopard ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Positive Staining ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies ◽  
Hairy Cells

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces complete remissions in 85% of patients. Complete remission has been defined as the absence of hairy cells in the bone marrow after routine morphologic examination. To determine if hairy cells could be detected in complete remission bone marrows using immunohistochemical techniques with antibodies L26 (CD20) and DBA.44, 154 bone marrow biopsies performed between 3 months and 25 months after therapy were studied. Of the biopsies, 50% exhibited staining with L26 and/or DBA.44 in five or more cells with morphologic features of hairy cells. Minimal residual disease was usually less than 1% of the total cellular population. DBA.44-positive cells were demonstrated in 91% of the biopsies, although in 48% of these the morphologic features of the positive cells were not sufficiently distinctive for hairy cells. The proportion of biopsies with residual hairy cells was similar over the 25 months of follow up, indicating a relatively stable amount of residual disease. Immunomorphologic analysis is a more sensitive method for detecting residual hairy cells than morphology alone. Although further follow up is necessary to determine the clinical significance of the L26/DBA.44-positive staining in cells with and without distinctive morphologic features of hairy cells, we conclude that many patients in a stable clinical remission may have residual hairy cells.

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.

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.

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 Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1556-1560 ◽  
Author(s):  
S Wheaton ◽  
MS Tallman ◽  
D Hakimian ◽  
L Peterson
Keyword(s):  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Hematoxylin And Eosin ◽  
Anti Cd20 ◽  
Minimal Residual

Minimal residual disease (MRD) can be detected in bone marrow core biopsies of patients with hairy cell leukemia (HCL) after treatment with 2-chlorodeoxyadenosine (2-CdA) using immunohistochemical (IHC) techniques. The purpose of this study was to determine whether the presence of MRD predicts bone marrow relapse. We studied paraffin- embedded bone marrow core biopsies from 39 patients with HCL in complete remission (CR) 3 months after a single cycle of 2-CdA. Biopsies performed 3 months posttherapy and annually thereafter were examined by routine hematoxylin and eosin (H&E) staining and IHC using the monoclonal antibodies (MoAbs) anti-CD45RO, anti-CD20, and DBA.44. At 3 months after therapy, 5 of 39 (13%) patients had MRD detectable by IHC that was not evident by routine H&E staining. Two of the five patients (40%) with MRD at 3 months have relapsed, whereas only 2 of 27 (7%) patients with no MRD and at least 1 year of follow up relapsed (P = .11). Over the 3-year follow-up period, two additional patients developed MRD. Overall, three of six (50%) patients with MRD detected at any time after therapy have relapsed, whereas only 1 of 25 (4%) patients without MRD has relapsed (P = .016). These data suggest that the presence of MRD after treatment with 2-CdA may predict relapse.

scholarly journals Detection of minimal residual disease by immunostaining of bone marrow biopsies after 2-chlorodeoxyadenosine for hairy cell leukemia

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1798-1802 ◽  
Author(s):  
D Hakimian ◽  
MS Tallman ◽  
C Kiley ◽  
L Peterson
Keyword(s):  
Minimal Residual Disease ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Additional Patient ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies ◽  
Hairy Cells ◽  
B Lineage ◽  
Minimal Residual

Abstract 2-Chlorodeoxyadenosine (2-CdA) yields high complete remission (CR) rates in patients with hairy cell leukemia (HCL). In an effort to detect minimal residual disease, we studied two B-lineage antibodies, L26 and MB2, and a T-lineage antibody, UCHL-1, in fixed marrow core biopsies from 34 patients with HCL before and after 2-CdA. Before therapy, hairy cells exhibited intense cytoplasmic membrane reactivity with L26 and strong intracytoplasmic reactivity with MB2. UCHL-1 did not react with hairy cells. Thirty-one patients were assessable 3 months after therapy. Five of 24 (21%) patients in CR by routine evaluation had residual HCL detected by immunostaining. Four of these 5 patients have been reevaluated at 1 year. One patient relapsed by routine evaluation, 2 remained positive by immunostaining alone, and 1 patient became negative by immunostaining. A total of 19 patients have been evaluated at 1 year. Only 1 additional patient has become positive by immunostaining alone. Immunostaining using the B-lineage antibodies highlighted the presence of hairy cells with preservation of morphology. This assisted in quantifying the extent of disease, particularly when hairy cells were interstitial and blended with surrounding hematopoietic tissue, when hairy cells were present in hypocellular marrows, when hairy cells were spindle-shaped, and when marrows were markedly fibrotic. Because immunostaining can be easily performed on routinely processed marrows, it is an attractive method to detect minimal residual disease. Our data suggest that some patients in apparent CR after 2-CdA may have minimal residual disease. Patients will need to be observed prospectively to determine if residual disease will be predictive of relapse.

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).

scholarly journals Detection of minimal residual disease by immunostaining of bone marrow biopsies after 2-chlorodeoxyadenosine for hairy cell leukemia

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1798-1802 ◽  
Author(s):  
D Hakimian ◽  
MS Tallman ◽  
C Kiley ◽  
L Peterson
Keyword(s):  
Minimal Residual Disease ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Additional Patient ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies ◽  
Hairy Cells ◽  
B Lineage ◽  
Minimal Residual

2-Chlorodeoxyadenosine (2-CdA) yields high complete remission (CR) rates in patients with hairy cell leukemia (HCL). In an effort to detect minimal residual disease, we studied two B-lineage antibodies, L26 and MB2, and a T-lineage antibody, UCHL-1, in fixed marrow core biopsies from 34 patients with HCL before and after 2-CdA. Before therapy, hairy cells exhibited intense cytoplasmic membrane reactivity with L26 and strong intracytoplasmic reactivity with MB2. UCHL-1 did not react with hairy cells. Thirty-one patients were assessable 3 months after therapy. Five of 24 (21%) patients in CR by routine evaluation had residual HCL detected by immunostaining. Four of these 5 patients have been reevaluated at 1 year. One patient relapsed by routine evaluation, 2 remained positive by immunostaining alone, and 1 patient became negative by immunostaining. A total of 19 patients have been evaluated at 1 year. Only 1 additional patient has become positive by immunostaining alone. Immunostaining using the B-lineage antibodies highlighted the presence of hairy cells with preservation of morphology. This assisted in quantifying the extent of disease, particularly when hairy cells were interstitial and blended with surrounding hematopoietic tissue, when hairy cells were present in hypocellular marrows, when hairy cells were spindle-shaped, and when marrows were markedly fibrotic. Because immunostaining can be easily performed on routinely processed marrows, it is an attractive method to detect minimal residual disease. Our data suggest that some patients in apparent CR after 2-CdA may have minimal residual disease. Patients will need to be observed prospectively to determine if residual disease will be predictive of relapse.

scholarly journals Minimal Residual Disease, Its Detection and Significance in Hairy-Cell Leukemia

1999 ◽  
Vol 42 (3) ◽  
pp. 85-88 ◽  
Author(s):  
Pavel Žák ◽  
Ladislav Chrobák ◽  
Karel Dědič
Keyword(s):  
Complete Remission ◽  
Minimal Residual Disease ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Hairy Cells ◽  
Minimal Residual

As minimal residual disease (MRD) is considered the detection of hairy cells (HCs) in a patient with hairy cell leukemia (HCL) in complete remission with the absence of detectable HCs by routine morphology of peripheral blood, aspirates and bone marrow core sections, using more sensitive methods of identification as immunohistological staining or polymerase chain reaction (PCR) to detect immunoglobulin heavy chain genes rearrangement. Various monoclonal antibodies (MoAbs) as CD20, DBA.44, B ly-7, HC2, CD25 and CD11c have been applied using immunological staining. There is no standardized technique for identification of MRD. According to the technique used the MRD has been detected in 13% to 100% of patients in complete remission (CR). It may be concluded that many patients, if not all, in stable CR may have residual HCs. Whether MRD will have impact on early relapse or on long term outcome, or whether patients in CR with persistant MRD will remain so, is a matter of a longer follow-up.

Potential Predictive Patterns of Minimal Residual Disease Detected by Immunohistochemistry on Bone Marrow Biopsy Specimens During a Long-term Follow-up in Patients Treated With Cladribine for Hairy Cell Leukemia

2006 ◽  
Vol 130 (3) ◽  
pp. 374-377 ◽  
Author(s):  
Paulette Mhawech-Fauceglia ◽  
Martin Oberholzer ◽  
Senait Aschenafi ◽  
Audrey Baur ◽  
Michael Kurrer ◽  
...  
Keyword(s):  
Complete Remission ◽  
Minimal Residual Disease ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Biopsy Specimens ◽  
Patients At Risk ◽  
Minimal Residual

Abstract Context.—Minimal residual disease (MRD) in patients treated for hairy cell (HC) leukemia as assessed by immunohistochemistry has not been included routinely in evaluation of treatment results. Objective.—To assess the presence of persistent HCs after treatment, as detected by immunohistochemistry, and to evaluate the correlation between the level of MRD and clinical outcome. Design.—Percentages of DBA.44-positive HCs were assessed on 116 biopsy specimens from 17 patients. The patients had a median follow-up of 55.4 months. Results.—Minimal residual disease was seen in 3 patterns. Group 1 (7 patients) had MRD levels ranging from “rare scattered suspicious HCs” to less than 1%. The MRD levels were stable throughout follow-up, and all patients remained in complete remission. Group 2 (6 patients) had MRD levels ranging from 1% to 5%, and 3 patients were in complete remission at 77.9, 63.8, and 108.0 months. Another patient showed evidence of disease activity (partial remission) at 47.6 months. Two other patients relapsed at 12.3 months and at 25.7 months, respectively, with greater than 1% HCs. Group 3 (4 patients) had MRD levels greater than 5%. Three patients relapsed at 11.3, 12.1, and 29.6 months, respectively, with greater than 5% HCs. The fourth patient had MRD levels of 5% at 14.6 months and 2% at 20.0 months but was subsequently lost to follow-up. Conclusions.—Quantitative assessment of MRD may be of value in identifying patients at risk for relapse of hairy cell leukemia.

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

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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