Emerging Consensus

Immediately after I finished writing and publishing my recent three part series on stem cell transplants, I came across this hot-off-the-presses review (July 29, 2009) “Blood” article by Peter Dreger et al. Dr. Dreger is a highly regarded CLL expert and I thought you should know what he and his collegues have to say on this very important subject.

The abstract of his article is below. (Send me a personal email if you want help locating the full text version of his article. It is detailed and very well written). I have also included several quotes from the Dreger article.

Much of the same ground has been covered in Part – I & II of my recently published transplant series, so much so that I do not think this article requires additional editorial comments from me. Nevertheless, it is remarkable that finally (!!) we are getting consensus on patient selection and timing of stem cell transplantation of CLL patients with aggressive disease.  Heck, at this rate we might even be able to convince our insurance companies to cover the cost of these expensive procedures, by waving articles such as this under their noses!

Too many local practitioners (and even experts who have not kept up with the latest information) are ill informed about recent advances in stem cell transplants all the more reason why we as patients have to be better informed on the subject, to be proactive in our conversation with our doctors and get a second or third opinion if our first line physicians are not familiar with recent developments on treatment of this “good” cancer that is all too often an incurable and killer cancer.

Please bear in mind “RIC” or “reduced intensity conditioning” allogeneic transplants are the same as “mini-allo” transplants.

Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for primetime?

Delgado J, Milligan DW, Dreger P.

Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

The development of reduced intensity conditioning (RIC) regimens has increased the number of patients diagnosed with chronic lymphocytic leukemia (CLL) that are referred for allogeneic hematopoietic cell transplantation (allo-HCT). However, given the toxicity of allo-HCT, it should only be offered to eligible patients whose life expectancy is significantly reduced by the disease. Accordingly, the European Group of Blood and Marrow Transplantation has recently identified those patients in whom allo-HCT could be a reasonable therapeutic approach. In this review, we have evaluated the outcome of CLL patients undergoing allo-HCT, either after conventional or RIC regimens, in the context of current non-transplant strategies. We have also analyzed the most important predisposing factors that might interfere with the procedure as well as post-transplant complications that are particularly common in these patients. Finally, we have addressed the most relevant factors when deciding what patients should be considered for allo-HCT and the timing of the procedure.

PMID: 19641189

Quotes from Dreger et al:

You really should read the well written full text article.  There are some very nice tables comparing efficacy of various conventional approaches as well as transplant protocols.

  • Use of autologous HCT, which solely relies on dose intensity and does not appear to be curative in CLL, is rapidly declining with the advent of modern immunochemotherapy.
  • 50% of CLL patients with early-stage disease eventually die of disease progression or disease-related complications, and almost all patients younger than 55 years at the time of diagnosis invariably die of their disease regardless of clinical stage.
  • patients whose tumor cells have specific biologic characteristics, such as the presence of a deletion in the short arm of chromosome 17, not only have a poor prognosis, but also are more frequently refractory to conventional chemotherapy and might benefit from alternative treatment strategies.
  • Even modern chemo-immunotherapy combinations, e.g. fludarabine, cyclophosphamide and rituximab (FCR), able to achieve objective responses in 95% of patients when given is initial treatment, have a long-term progression-free survival (PFS) around 50% at six years with no plateau in the curve. Furthermore, these impressive responses are costly in terms of early and late toxicity.
  • patients with fludarabine refractory disease or 17p deletion have a poor outcome without transplantation, with a median PFS (progression free survival) of 11-15 months and a median OS (overall survival) of 12-40+months. Comparatively, the results obtained with RIC allo-HCT are apparently better.
  • evidence that myeloablative conditioning is superior to RIC, even in younger or patients with fewer co-morbidities, is lacking, although a potential role of conditioning intensity in patients with refractory/bulky disease or HLA-mismatched donor-recipient pairs cannot be excluded.
  • CLL was one of the diseases that benefited most from the implementation of RIC transplantation programs.
  • Patients with bulky lymphadenopathy (> 5 cm) at the time of transplantation had a particularly poor outcome, with a 5-year relapse rate and PFS of 71% and 8%, respectively
  • If a CLL patient is eligible for RIC allo-HCT and has a donor available, he/she should proceed to transplantation as soon as EBMT criteria are met.
  • Patients who can expect a significant reduction of life expectancy under alternative therapies should be promptly identified and referred for allo-HCT before the disease becomes unresponsive to salvage treatment, provided there is a related or unrelated donor available.
  • Because of the potent GVCLL effect, allogeneic HCT is a very powerful tool in the management of poor risk CLL patients, but there is room for improvement.