Resolution of Hairy Cell Leukemia Minimal Residual Disease by Both BRAF and Clone-Specific Real-Time Quantitative PCR (RQ-PCR) After Treatment with Moxetumomab Pasudotox.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2896-2896 ◽  
Author(s):  
Robert J. Kreitman ◽  
Evgeny Arons ◽  
Sapolsky Jeffrey ◽  
Laura Roth ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Specific Primer ◽  
Minimal Residual

Abstract Abstract 2896 Background: Moxetumomab pasudotox is an anti-CD22 recombinant immunotoxin containing truncated Pseudomonas exotoxin which was recently reported to achieve a complete remission rate of 46% in 28 patients with relapsed/refractory hairy cell leukemia (HCL). An additional 20 patients were treated at the highest dose level and are now fully evaluable for response and minimal residual disease (MRD) determinations. RQ-PCR using clone-specific primers and a clone-specific TaqMan probe is capable of detecting one HCL cell in 106normal cells. Recently reported methods to detect the HCL-associated BRAF V600E mutation include pyrosequencing (5–10% sensitivity) and PCR (0.1–0.23% sensitivity). Methods: Moxetumomab pasudotox was administered to 16 patients at 5–40 ug/Kg every other day for 3 doses (QODx3) and to 32 patients at 50 ug/Kg QODx3, via 1–16 (median 4) cycles per patient at 4-week intervals. Complete remission (CR) required resolution of cytopenias and elimination of HCL in the blood and marrow by standard microscopy, but MRD could be present by flow cytometry of blood or bone marrow aspirate (BMA) or immunohistochemistry (IHC) of the bone marrow biopsy (BMBx). Blood and marrow from patients were also tested by PCR using consensus primers. When immunoglobulin (Ig) rearrangements could be cloned, RQ-PCR using clone-specific primer and probe was performed. To detect MRD by the BRAF V600E mutation, BRAF quantitative PCR (BRAF-qPCR) was performed on cDNA samples, using mutant-specific primer, and SYBR-Green detection followed by melting point analysis. MRD testing for BRAF-qPCR, unlike clone-specific RQ-PCR, did not require prior cloning of the Ig rearrangement. Results: All 198 cycles of moxetumomab administered to 48 patients were evaluable for toxicity and response. No dose limiting toxicity was observed, although 2 patients as previously reported had a grade 2 hemolytic uremic syndrome with transient grade 1 platelet and creatinine abnormalities. Of the 48 HCL patients at all dose levels, there were 26 (54%) CRs, with an overall response rate (ORR) of 88%. Of 32 at 50 ug/Kg QODx3, there were 19 (59%) CRs with an ORR of 91%. Of these 19 CRs, 11 (58%) achieved MRD negativity by repeated flow cytometry of both BMA and blood and IHC of BMBx. Flow cytometry of the BMA was the most sensitive conventional test of MRD. Of the 9 CRs at 50 ug/Kg QODx3 evaluable by clone-specific RQ-PCR of blood, 5 negative were also flow-negative, and 4 positive were also flow-positive (p=0.008). BRAF-qPCR on cDNA from limiting dilutions of BRAF V600E+ Colo-205 cells into BRAF wild-type cells achieved consistent detection at 1:105dilution (0.001%). Of 10 flow-negative CRs at 50 ug/Kg QODx3 evaluated by BRAF-qPCR, all 10 (100%) were BRAF-qPCR negative, including 4 which were nonevaluable by RQ-PCR due to inability to clone the Ig rearrangements prior to treatment. Currently 12 (63%) of the 19 CRs at 50 ug/Kg QODx3 are ongoing at 6–47 (median 21) months, including 10 (91%) of 11 MRD-negative vs 2 (25%) of 8 MRD+ CRs (p=0.006). Conclusions: Moxetumomab pasudotox is active in relapsed and refractory HCL and has a safety profile supporting further development for this disease. Retreatment on this trial could not necessarily be extended to achieve MRD-negative BMAs or molecular remission by RQ-PCR using sequence-specific or BRAF primers. However, these tests might be useful in the future to guide retreatment, optimize CR durability and possibly eradicate the HCL clone in selected patients. This summary contains investigator reported data. This study was sponsored by MedImmune, LLC, and supported by NCI's Intramural Research Program and the Hairy Cell Leukemia Research Foundation. Disclosures: Kreitman: NIH: Co-inventor on the NIH patent for Moxetumomab Pasudotox, Co-inventor on the NIH patent for Moxetumomab Pasudotox Patents & Royalties. Off Label Use: Moxetumomab Pasudotox is an experimental agent for CD22+ hematologic malignancies. FitzGerald:NIH: Coinventor on the NIH patent for Moxetumomab Pasudotox, Coinventor on the NIH patent for Moxetumomab Pasudotox Patents & Royalties. Fei:AstraZeneca: Stock, Stock Other; MedImmune, LLC: Employment. Ibrahim:AstraZeneca: Stocks, Stocks Other; MedImmune: Employment. Pastan:NIH: Coinventor on NIH patent for moxetumomab pasudotox, Coinventor on NIH patent for moxetumomab pasudotox Patents & Royalties.

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.

Evaluation of BRAFV600E, NRAS and KRAS Mutations As Well As IGHV Usage for Diagnostic Use in Hairy Cell Leukemia, Hairy Cell Leukemia-Variant and Splenic Marginal Zone Lymphoma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2679-2679
Author(s):  
Susanne Schnittger ◽  
Frank Dicker ◽  
Christiane Eder ◽  
Sabine Jeromin ◽  
Tamara Alpermann ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Leukemic Cells ◽  
Multiparameter Flow Cytometry ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Equity Ownership

Abstract Abstract 2679 Background: The BRAF V600E mutation has recently been discovered in nearly all cases of hairy cell leukemia (HCL), but not in cases of HCL-variant (HCL-v). However, this perfect correlation has been challenged by studies reporting HCL cases without BRAF V600E. Interestingly, the immunoglobulin heavy chain variable region gene IGHV4–34, which has been associated with poor prognosis in HCL, appeared exclusively and to a high percentage in these BRAF V600E-negative cases of classic HCL and also in HCL-v (Xi et al., Blood, 2011). Further, splenic marginal zone lymphoma (SMZL) is a disease closely related to HCL and HCL-v and BRAF has been shown to be unmutated in this entity. Aims: 1. To characterize our cohorts of HCL, HCL-v and SMZL for the presence of BRAF V600E and to correlate the results with IGHV gene usage. 2. We hypothesized that other genes of the RAF/RAS pathway might be affected. Thus we analysed NRAS, and KRAS in addition to BRAF for mutations in all three entities. Methods: We analyzed the bone marrow or peripheral blood of 314 cases (182 cases with HCL, 49 cases with HCL-v, and 83 cases with SMZL) at diagnosis as confirmed by multiparameter flow cytometry and cytomorphology. The BRAF V600E mutation was analyzed by an mRNA-based reverse transcription allele-specific real-time quantification (RQ-PCR) assay. The BRAF V600E expression was calculated as %BRAF V600E/BRAF wt. NRAS and KRAS were analyzed by melting curve analysis and subsequent Sanger sequencing. IGHV genes and mutation status were analyzed by the use of Biomed-2 primers. An identity of ≥98% of the analyzed IGHV sequence compared to published germline sequences was considered an unmutated IGHV status. Results: In our cohort the median percent leukemic cells was 16% (range 0.2–74%) for HCL, 33% (range 5–59%) for HCL-v and 29% (range: 1–84%) for SMZL as determined by multiparameter flow cytometry. The BRAF V600E mutation was detected in 178/182 (97.8%) of HCL cases, whereas 0/49 of HCL-v and 0/83 SMZL were positive. Thus, the BRAF V600E mutation is 100% specific for HCL regarding these three entities. The median BRAF V600E expression ratio of positive cases was 14.2 (range 0.22 – 280.3). After normalization to % pathological cells as assessed by multiparameter flow cytometry the median ratio was 173 (range:22–1,788). However, in 4 cases with 4%, 8%, 28% and 66% percent leukemic cells by multiparameter flow cytometry, which is within the clone size that can be clearly detected by the BRAF V600E-specific RQ-PCR assay, no mutation was detected. Thus, BRAF V600E detection used for the identification of HCL has a sensitivity of 97.8%. Further, NRAS and KRAS mutation screening in all cases with HCL, HCL-v, and SMZL did not detect any mutation except for one case with SMZL that harboured an NRAS Gly12Asp mutation. This case was found to have an MDS in parallel and thus the mutation more likely belongs to the MDS clone. Thus, analysis of NRAS and KRAS mutations does not further improve diagnostics in these diseases. Further, we analyzed the IGHV usage in all 4 BRAF unmutated HCL and in additional 60 cases (total n=64) with HCL and 41 cases with HCL-v. IGHV4–34 usage was very frequent in HCL-v with 14/41 (34.1%). In contrast, it was never detected in HCL including the BRAF wildtype cases. Thus, we were not able to confirm the usage of the IGHV4–34 gene, which was previously suggested for BRAF V600E negative HCL. On the other hand IGHV5–51 was most frequently found in HCL (9/64, 14.1%) but never detected in HCL-v. We detected an unmutated IGHV status in 12/62 (19.4%) of HCL, which was less frequent compared to 14/40 (35.0%) in HCL-v (p = 0.095). The IGHV mutation status was unmutated in 9/11 (81.8%) IGHV4–34 cases (100% identity to germline each). The four cases of HCL, which lacked BRAF V600E mutation, expressed the IGHV genes IGHV1–3*01 (96.5% identity), IGHV1–69*02 (94.0% identity), IGHV3–9*01 (96.9% identity) and IGHV6-1*01 (99.0% identity), which were also expressed by various BRAF V600E positive HCL cases in our cohort. Conclusions: 1) In our cohort of 314 cases with HCL, HCL-v, and SMZL we confirm a high specificity (100%) and sensitivity (97.8%) for BRAF V600E mutations to detect HCL. 2) Other RAS pathway mutations (NRAS, KRAS) were not detected in any of the three analysed entities. 3) In the 4 rare cases of HCL with BRAF wt we were not able to confirm the previously postulated IGHV4–34 usage. 4) IGHV4–34 further delineates classic HCL from HCL-v. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Equity Ownership. Dicker:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Jeromin:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership.

Co-Treatment Of Hairy Cell Leukemia and Melanoma With The BRAF Inhibitor Dabrafenib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5311-5311 ◽  
Author(s):  
Leslie A. Andritsos ◽  
James S. Blachly ◽  
Kari Kendra ◽  
Gerard Lozanski ◽  
Michael R. Grever
Keyword(s):  
Bone Marrow ◽  
Malignant Melanoma ◽  
Hairy Cell Leukemia ◽  
Braf Mutation ◽  
Braf Inhibitor ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Marrow Cellularity

Abstract The activating BRAF mutation V600E has been identified in many human cancers, including colon and lung adenocarcinoma, papillary thyroid cancer, malignant melanoma, and hairy cell leukemia. Here we report for the first time treatment of hairy cell leukemia and malignant melanoma both harboring the BRAF V600E mutation with the BRAF inhibitor dabrafenib. The patient is a 67-year-old man with a history of classic hairy cell leukemia (immunophenotype CD11c, CD19, CD20 (bright), CD25, and CD103). At the time of diagnosis he had pancytopenia and received therapy with cladribine 0.12 mg/kg/day as a 2 hour infusion daily for 5 days, achieving a complete hematologic remission (CHR). His disease recurred 2 years later and he was again treated with cladribine 0.9 mg/kg/day as a 7 day continuous infusion, achieving a CHR. He remained in remission for 5 years, and this time received salvage therapy with pentostatin 4 mg/m2 every 2 weeks for a total of 12 doses. He achieved a CHR with minimal residual disease on bone marrow biopsy (0.3% of lymphocytes). He also had dyserythropoiesis concerning for myelodysplastic syndrome in addition to neurologic toxicity with gait imbalance. He was managed expectantly for the next 2 years, during which time he developed an 8 mm red nodule on the extensor surface of his right forearm, and a shave biopsy showed nodular melanoma, Clark’s level IV. He underwent a wide local excision with a negative axillary sentinel lymph node biopsy followed by adjuvant sargramostim (GM-CSF) for 12 months. His melanoma then recurred at the site of the prior excision. A PET scan showed an additional lesion in the midportion of the right arm. The excised solitary recurrence was sent for BRAF V600E mutation testing, which was positive. He received a course of radiotherapy (30 Gy over 14 days) to the affected limb, after which he had no evidence of disease. During this time, he was found to have worsening thrombocytopenia and splenomegaly, as well as a rising IL2 receptor level (peak 3952 U/mL; normal < 970), while bone marrow biopsy showed a 20% cellular marrow with 40% involvement by classic HCL. BRAF testing of the bone marrow by Sanger sequencing was positive for the V600E mutation. Because both his HCL and melanoma harbored the BRAF V600E mutation, the patient was eligible for and enrolled on a phase I clinical trial of dabrafenib for BRAF V600E mutant malignancies. Dabrafenib was initiated orally at a dose of 150 mg twice daily. Each cycle was 28 days. After 3 cycles, the bone marrow cellularity had improved to 30% with a decrease in the leukemic content to 10-15% of marrow cellularity. After 6 cycles, the bone marrow cellularity was normal for age with no residual HCL detectable by immunohistochemical stains or flow cytometric immunophenotyping. PET/CT scan at this time demonstrated no FDG avid lesions and no splenomegaly. Toxicites have consisted of characteristic RAF-associated skin changes and one instance of squamous cell carcinoma, which was excised. He has otherwise had no side effects from therapy. The patient has now completed 12 cycles of therapy with dabrafenib without evidence of either HCL or melanoma. He will remain on therapy as long as he is deriving clinical benefit per protocol. Given the increased risk of second primary malignancies in HCL, BRAF mutation testing should be considered for patients developing solid tumors in which this has been described, as co-treatment may be possible. Disclosures: Off Label Use: Dabrafenib for treatment of hairy cell leukemia. Kendra:Glaxo Smith-Kline: Research Funding.

scholarly journals Long Term Follow-up of a Phase II Study of Cladribine with Concurrent Rituximab in Patients with Hairy Cell Leukemia Variant

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1536-1536
Author(s):  
Dai Chihara ◽  
Evgeny Arons ◽  
Maryalice Stetler-Stevenson ◽  
Constance M. Yuan ◽  
Hao-Wei Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Purine Analog ◽  
Minimal Residual

Background Hairy cell leukemia (HCL) variant (HCLv) is considered a separate, more aggressive entity compared to classic HCL. HCLv responds poorly to single-agent purine analog with complete response (CR) rates below 10% and overall response rates under 50%. Rituximab combined with purine-analog can improve response rate and duration, but long-term data have not been reported for HCLv, particularly regarding minimal residual disease (MRD). We therefore update the results of a phase II trial with cladribine and concurrent rituximab in patients with HCLv, previously reported for 10 of the 20 patients enrolled. Methods Patients with HCLv with 0 to 1 prior courses of cladribine, and/or 0-1 prior courses of rituximab, received cladribine (0.15 mg/kg days 1-5), with 8 weekly doses of rituximab (375 mg/m2) beginning day 1. The primary endpoint was to determine CR rate and secondary endpoints included evaluating minimal residual disease (MRD) by blood and bone marrow aspirate flow cytometry, and bone marrow biopsy immunohistochemistry. Patients were able to receive a 2nd course of rituximab ≥ 6 months after the first, if and when MRD was detected in blood. Results Twenty patients were enrolled. Median age was 67 (range: 42-86) years. No patients had prior concurrent cladribine-rituximab. Eight were previously untreated, 1 had only splenectomy, 6 had prior cladribine, 1 had prior cladribine and splenectomy, 1 had prior rituximab, 1 had prior rituximab and splenectomy, 1 had cladribine, rituximab, and splenectomy, and 1 had combination rituximab-containing chemotherapy followed by cladribine. Out of 20 patients receiving concurrent cladribine-rituximab (CDAR), the CR rate was 95% (95% CI: 75-100%). This CR rate was superior to a historical control group of 3 of 39 HCLv patients who achieved CR to cladribine alone (p&lt;0.0001). Sixteen (80%, 95% CI: 56-94%) of 20 patients became MRD-free at 6 months; median duration of MRD-free CR was 72.0 months, with 9 of 16 still MRD-free at 5-108 (median 29.1) months. With median potential follow up of 88 months (range: 7-123 months), 10 patients received delayed rituximab and 4 re-achieved MRD-free CR. Six patients required alternative treatment and 6 patients died, 5 with HCLv including 1 with HCLv limiting treatment for lung cancer, and 1 with Parkinson's disease but still MRD-free. Time from progression of HCLv to death was 5.9-30.0 (median 28.1) months. Achieving MRD-free CR by 6 months after CDAR (16 vs 4 patients) was important for median progression free survival [PFS, unreached vs 17.4 mo, hazard ratio (HR) 0.031, 95% CI 0.003-0.29, p&lt;0.0001] and overall survival (OS, unreached vs 38.2 months, HR infinite since all 4 MRD+ deaths were prior to deaths of 2 patients who achieved MRD-free CR, p&lt;0.0001). A significant relationship between prior purine analog therapy or unmutated IGHV4-34 (n=7) status and either PFS or OS has not yet been observed. Conclusion Concurrent cladribine with rituximab is highly effective in HCLv irrespective of prior purine-analog treatment or IGHV4-34 status and should replace purine analog monotherapy as treatment. Patients with long-term MRD-free CR are being followed to determine whether concurrent cladribine-rituximab as 1st-3rd line systemic therapy can permanently eradicate HCLv. Patients who progress have limited OS. This provides a rationale for the testing of higher intensity approaches up front and the identification of additional treatment options for HCLv. Disclosures Kreitman: Genentech: Research Funding. OffLabel Disclosure: Rituximab for hairy cell leukemia

Identification of the BRAF V600E mutation in Japanese patients with hairy cell leukemia and related diseases using a quenching probe method

2018 ◽  
Vol 108 (4) ◽  
pp. 416-422
Author(s):  
Hidekazu Itamura ◽  
Masaru Ide ◽  
Akemi Sato ◽  
Naoko Sueoka-Aragane ◽  
Eisaburo Sueoka ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Japanese Patients ◽  
Braf V600e Mutation ◽  
Probe Method ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Quenching Probe

scholarly journals Usefulness of Dual Immunohistochemistry Staining in Detection of Hairy Cell Leukemia in Bone Marrow

2019 ◽  
Vol 153 (3) ◽  
pp. 322-327 ◽  
Author(s):  
Gaurav K Gupta ◽  
Xiaoping Sun ◽  
Constance M Yuan ◽  
Maryalice Stetler-Stevenson ◽  
Robert J Kreitman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Predictive Value ◽  
Lymphoid Cells ◽  
Multiparameter Flow Cytometry ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Flow Cytometry Data ◽  
Flow Cytometric Data

Abstract Objectives We evaluated efficacy of two dual immunohistochemistry (IHC) staining assays in assessing hairy cell leukemia (HCL) involvement in core biopsies and compared the results with concurrently collected flow cytometric data. Methods Overall, 148 patients with HCL (123 male, 25 female; mean age: 59.8 years; range: 25-81 years) had multiparameter flow cytometry performed using CD19, CD20, CD22, CD11c, CD25, CD103, CD123, surface light chains, CD5, and CD23. In parallel, bone marrow IHC was done using PAX5/CD103 and PAX5/tartrate-resistant alkaline phosphatase (TRAP) dual IHC stains. Results Overall sensitivity of dual IHC stains was 81.4%, positive predictive value was 100%, and negative predictive value was 81.7%. All IHC-positive cases concurred with flow cytometry data, even when HCL burden was extremely low in the flow cytometry specimens (as low as 0.02% of all lymphoid cells). Conclusions Dual IHC stain is a sensitive tool in detecting HCL, even in cases with minimal disease involvement.

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 Hairy cell leukemia with CCND1/IGH fusion gene and BRAF V600E mutation

2020 ◽  
Vol 13 ◽  
pp. 100197 ◽  
Author(s):  
Zaid Abdel Rahman ◽  
Firas Muwalla ◽  
Liuyan Jiang ◽  
James Foran
Keyword(s):  
Hairy Cell Leukemia ◽  
Fusion Gene ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia
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