Blood First Edition Paper, prepublished online August 10, 2009; DOI 10.1182/blood-2009-03-212449.
Hairy cell leukemia (HCL) is generally responsive to single-agent Cladribine and only a minority of patients are refractory and with poor prognosis. HCL generally express mutated (M) and, in a minority, unmutated (UM) immunoglobulin-heavy-chain-variable-region-genes (IGHV). In a multicenter clinical trial in newly diagnosed HCL, we prospectively investigated clinical and molecular parameters predicting response and event-free survival (EFS) after single-agent Cladribine. Of 58 HCL, 6 expressed UM-IGHV (UM-HCL) and 52 M-IGHV (M-HCL). Beneficial responses were obtained in 53/58 patients (91%), while treatment failures were observed in 5/58 (9%) patients. Failures associated significantly with UM-IGHV (5/5 failures vs 1/53 beneficial responses had UM-IGHV, p<.0001), leucocytosis (3/5 vs 3/53, p=.006), and bulky spleen (4/5 vs 4/53, p=.0008). The UM-HCL not benefiting from Cladribine characteristically had bulky spleen (4/5, 80%), leukocytosis (3/5, 60%) and TP53 defects (2/5, 40% vs 0/53 UM/M-HCL benefiting from Cladribine, p=.006), and progressed rapidly after first treatment (median EFS 7.5 months). Our data suggest that UM-HCL identify the minor subgroup failing Cladribine treatment and with more aggressive disease. High incidence of TP53 disfunction indicates a potential mechanism of resistance to Cladribine in the UM-HCL group. Overall, our data provide new molecular elements relevant for treatment concerns in HCL.
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3 comments:
Greg, I just found your blog for the first time, but wasn't sure if your blog was about PAO and HCL or just PAO. I was diagnosed with HCL April of 2007 at age 68 after having radioactive seeding for prostate cancer August 2005, but the HCL was probably with me before the prostate cancer. I will also have to have a degenerating hip replaced in due time which probably came about because of 25 years of long-distance running. Fortunately, I can still mountain bike which I do on a regular basis except now on paved trails instead of risky single-track trails. I often wonder if both my prostate cancer and HCL had any connection to my exposure to Agent Orange which I recently discovered was in use during my tour of duty on Okinawa 1961-63 as well as in the Canal Zone where I was assigned the summer of 1964. Enjoyed reading your blog. I also read a blog called "Jon's Blog", Jon being treated for HCL at NIH earlier this year. I've been seeing my oncologist every 3 months since early 2007, but CBC counts have remained flat, albeit well below minimum range, so no chemotherapy recommended yet. Good luck to you on your recovery.
Jim Corbett (mozartplayer@gmail.com)
Grand Rapids, Michigan
Hi ,
This is for Greg and Jim.. If you would like to discuss HCL, email me at my email address.. I have had HCL for 15 years and am fairly well versed on the subject.
Greg, I was diagnosed at 43 and had it for about 2 years before diagnosis.
I speak to other HCL people through Leukemia & Lymphoma Society as well. There are a couple of things that you might be interested in.
This is for Jeff. I just now read your comment of 10/18/09, but I couldn't find your email address and wonder if you could email it to me at mozartplayer@gmail.com. I have a couple questions regarding your long-time experience with HCL. I recently learned that Agent Orange was in use during my 18 months of duty on the island of Okinawa 1961-63 and I now read that the VA has added HCL to its very growing list of diseases presumed to be caused by Agent Orange, one disease on the list being prostate cancer for which I was diagnosed and treated shortly before HCL was diagnosed although I very likely had HCL long before the prostate cancer. Four years later, I still don't require chemo according to my oncologist although CBC counts are all still down, but flat over time.
Would very much appreciate your email address. Thanks in advance.
Jim Corbett
Grand Rapids, Michigan
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