Phase II study of cladribine (2CDA) followed by rituximab for eradication of minimal residual disease (MRD) in hairy cell leukemia (HCL)

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 6620-6620 ◽  
Author(s):  
F. Ravandi-Kashani ◽  
H. Kantarjian ◽  
S. Verstovsek ◽  
C. Koller ◽  
S. Faderl ◽  
...  
Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1556-1560 ◽  
Author(s):  
S Wheaton ◽  
MS Tallman ◽  
D Hakimian ◽  
L Peterson

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.


Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1798-1802 ◽  
Author(s):  
D Hakimian ◽  
MS Tallman ◽  
C Kiley ◽  
L Peterson

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.


2003 ◽  
Vol 119 (2) ◽  
pp. 213-217 ◽  
Author(s):  
Justin E. Sausville ◽  
Rita G. Salloum ◽  
Lynn Sorbara ◽  
Douglas W. Kingma ◽  
Mark Raffeld ◽  
...  

1995 ◽  
Vol 21 (2) ◽  
pp. 142-151 ◽  
Author(s):  
Günther Konwalinka ◽  
Michael Schirmer ◽  
Wolfgang Hilbe ◽  
Falko Fend ◽  
Francoise Geisen ◽  
...  

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1798-1802 ◽  
Author(s):  
D Hakimian ◽  
MS Tallman ◽  
C Kiley ◽  
L Peterson

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.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 7079-7079 ◽  
Author(s):  
Robert J. Kreitman ◽  
Evgeny Arons ◽  
Katherine Still ◽  
Martin S. Tallman ◽  
Maryalice Stetler-Stevenson ◽  
...  

Blood ◽  
2010 ◽  
Vol 115 (10) ◽  
pp. 1893-1896 ◽  
Author(s):  
Darren S. Sigal ◽  
Robert Sharpe ◽  
Carol Burian ◽  
Alan Saven

Abstract Cladribine induces protracted remissions in patients with hairy cell leukemia (HCL). However, many long-term responders ultimately relapse. We sought to determine whether long-term complete responders subsequent to a single 7-day course of cladribine were without minimal residual disease (MRD) and potentially cured of HCL. From the 358-person Scripps Clinic cladribine database, we identified 19 patients in continuous and complete hematologic response (median age, 75 years; median time from diagnosis, 18 years; and median time from cladribine, 16 years). Nine of 19 (47%) patient samples had no evidence of residual disease; 7 of 19 (37%) samples had MRD; and 3 of 19 (16%) had morphologic evidence of HCL in hematoxylin and eosin–stained bone marrow sections. These results indicate that HCL is potentially curable after cladribine treatment. In addition, patients with MRD and even gross morphologic disease can live many years without manifesting hematologic relapses.


1999 ◽  
Vol 42 (3) ◽  
pp. 85-88 ◽  
Author(s):  
Pavel Žák ◽  
Ladislav Chrobák ◽  
Karel Dědič

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.


2006 ◽  
Vol 130 (3) ◽  
pp. 374-377 ◽  
Author(s):  
Paulette Mhawech-Fauceglia ◽  
Martin Oberholzer ◽  
Senait Aschenafi ◽  
Audrey Baur ◽  
Michael Kurrer ◽  
...  

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.


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