The ‘Bloody’ Details
Cord bloody details that is. Today seems to be my day for bad puns. I promised you we will be giving all the gory details (ahem) as we go along, signposts that may be of help to future travellers down the same path.
In the months ahead Harvey will be participating in an important clinical trial. Here is the official link to it. I also have detailed patient information / consent forms and other stuff for this clinical trial, for those interested in that level of detail. University of Minnesota has become the lead institution in the area of cord blood transplants for adults, hence Harvey’s trip up to Minneapolis before the end of this week. The ‘Minnesota double cord protocol’ results reported in a detailed 2007 paper in “Blood” established the yardstick by which all other protocols will be judged. The abstract of the paper is below, write to us if you want help locating the full text version of it.
Blood. 2007 Oct 15;110(8):3064-70. Epub 2007 Jun 14.
Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease.
Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR, McGlave PB, Wagner JE.
Blood and Marrow Transplant Program,
University of Minnesota, . firstname.lastname@example.org Minneapolis MN, USA
We evaluated the efficacy of umbilical cord blood (UCB) in the setting of a nonmyeloablative regimen consisting of fludarabine (200 mg/m2), cyclophosphamide (50 mg/kg), and a single fraction of total body irradiation (200 cGy) with cyclosporine and mycophenolate mofetil for posttransplantation immunoprophylaxis. The target cell dose for the UCB graft was 3.0 x 10(7) nucleated cells/kg, resulting in the selection of a second partially human leukocyte antigen-matched UCB unit in 85%. One hundred ten patients with hematologic disease were enrolled. Neutrophil recovery was achieved in 92% at a median of 12 days. Incidences of grades III and IV acute and chronic graft-versus-host disease (GVHD) were 22% and 23%, respectively. Transplantation-related mortality was 26% at 3 years. Survival and event-free survival (EFS) at 3 years were 45% and 38%, respectively. Favorable risk factors for survival were absence of high-risk clinical features (Karnofsky 50-60, serious organ dysfunction, recent fungal infection, P < .01) and absence of severe GVHD (P = .04), and favorable risk factors for EFS were absence of high-risk clinical features (P < .01) and use of 2 UCB units (P = .07). These findings support the use of UCB after a nonmyeloablative conditioning as a strategy for extending the availability of transplantation therapy, particularly for older patients.
Harvey did his due diligence before making up his mind, by visiting and interviewing researchers at most of the institutions doing adult cord blood transplants in this country. There is real excitement in this area and lots of good concepts are finally making it to the clinical trial stage. I have no doubt that at least some of them will change the landscape for all transplants in the years to come. In future posts I will tell you about some of them. But Harvey decided the best fit for him is the U of Minn double cord program. Dr. Dan Weisdorf (one of the authors of the article above) is his physician. He is also the head of the adult transplant program at U of Minn. Following up on the definitive 110 patient trial reported in the ‘Blood’ article above, Minnesota is taking the lead in a multi-center and large scale study of their protocol. A whopping 320 patients will be recruited. Age cut off is 69 years, and CLL patients are eligible. Want more details? Write to us.
Patient participation in clinical trials is at an all time low in this country – for a variety of reasons. Yet, this is the lifeline for new research, no progress is possible without well conducted and credible clinical trials. I have always felt the patients who participate in clinical trials are true heroes and people who walk in their shoes years later owe them a debt of gratitude. Win, draw or lose, now Harvey too joins the ranks of patient pioneers. Whether he gets that most coveted cure of his CLL or not, by the very process of participating in this clinical trial and bringing attention to the technology by virtue of maintaining this journal, in my book he is already a winner and a champion. Way to go Harvey!
Next week Harvey will go through every blood test known to man, bone marrow biopsy, CT scan, chest X-ray, lung function test, cardiac tests, general fitness tests (“Karnofsky performance” test), and consultations with transplant researchers, nurse practitioners, social workers, psychiatrists, housing counselors, and others that I have forgotten to mention. The idea is to have a complete picture of his physical status prior to kickoff. I have little doubt he will ace all the physical performance tests, since he just got back from a strenuous 6 mile mountain hike that whupped the angst out of his frisky dog EGCG. It will be interesting to see what the CT scan has to say on the status of hidden lymph nodes deep within his abdomen. I am keeping my fingers crossed none of them will be bigger than 2-3 cm – a big change from ‘larger than 5 cm’ bulky nodes he had before starting Humax-CD20 + fludarabine followed by Revlimid therapy. There is a definite correlation between bulky disease just before transplant and risk of relapse after, and I really don’t want Harvey to be at the short end of the stick on that count.