The role of hematopoietic stem cell transplantation in chronic myeloid leukemia
Summary (2 min read)
Introduction
- Chronic myeloid leukemia (CML) has seen unprecedented changes over the last decade.
- The introduction of tyrosine kinase inhibitors (TKI) has changed the outlook for patients with this previously uniformly fatal disease.
- If any, it is considered by many as tool of last resort when everything else has failed.
- This phenomenon is not restricted to CML.
- Still, HSCT is the most powerful intervention; it holds the potential for “cure” and outcome has dramatically improved over the last years [15, 16].
Evolution of HSCT for CML
- Historical perspective: the role model of CML for HSCT.
- The first allogeneic HSCT for CML was reported to the European Group for Blood and Marrow Transplantation (EBMT) database in 1975 from France, soon to be followed in 1978 by a patient from Switzerland and by 10 patients in 1979 from France, Italy, and the UK (personal communication; EBMT database, Leiden NL).
- They remained at a stable level in middle and low income countries where costs of drug therapy became higher than costs for a transplant [11, 19, 27–30].
- The first patient was reported to the EBMT database in 1979 from France, to be followed by 4 patients in 1980, from France as well.
- At least, a retrospective meta-analysis of six multicentre trials in Europe and the US showed no advantage of such a procedure compared to concurrent drug treatment [33].
Outcome of HSCT for CML
- Factors associated with outcome HSCT has been and still is associated with significant early and late transplant-related mortality.
- In the mid-eighties of last century, it became apparent that outcome was related to specific pretransplant criteria, independent of transplant technology.
- A recent comparison between the CML III and IIIA study clearly indicated a major improvement in outcome in the latter [51].
- No early excess mortality was noted [45].
- A retrospective meta-analysis of six studies showed no advantage for the patients with autologous HSCT; hence, autologous HSCT has been largely abandoned as treatment for patients with CML [33].
Current recommendations
- The current ELN recommendations consider allogeneic HSCT, define when a donor search should be undertaken, and recommend at given states allogeneic HSCT [50].
- “Allo SCT is recommended for all BP patients and for the AP patients who do not achieve an optimal response.”.
- They list HSCT among six types of standard treatment, targeted therapy, chemotherapy, biologic therapy, high-dose chemotherapy with stem cell transplant, donor lymphocyte infusion (DLI), and surgery, without specifications.
- But most focus with few exceptions primarily on disease risk.
- Transplant risk, with the exception of the UK recommendation is vaguely specified.
Concluding remarks
- The introduction of TKI as targeted therapy has eased and improved the treatment of CML in an unprecedented way.
- Outcome of HSCT has substantially improved over the last decade, numbers of HLA typed unrelated donors has increased to more than 22 million worldwide and assessment of the likelihood to find a well-matched donor can be done today in a very short time.
- Continued drug therapy, experimental approaches, or palliation might be the wiser option.
- More patients will profit from a safe transplant; fewer patients will undergo a futile transplant procedure.
- The manuscript is solely written by the authors.
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Citations
53 citations
Cites background from "The role of hematopoietic stem cell..."
...As a consequence of these findings, more CML patients are now transplanted in second chronic or advanced phases than in first CP [67]....
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34 citations
Cites background from "The role of hematopoietic stem cell..."
...Since the advent of TKIs, HSCT is now recommended as second line or even third line therapy for CML patients, restricted to those who have failed multiple TKIs, or whom with very advanced disease [36, 37]....
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27 citations
Cites background from "The role of hematopoietic stem cell..."
...Significant efforts are underway to optimize allograft regimens, identify the determinants and mechanisms of relapse, and develop risk-adapted protocols before and after transplantation [34-37]....
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References
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Frequently Asked Questions (9)
Q2. What has shifted the community from major University centers towards decentralized medical practice?
The ease of drug administration has as well shifted the patient community from major University centers towards decentralized medical practice.
Q3. What is the role of HSCT in the treatment of CML?
Ease of application and improved response to modern drug therapy has almost halted HSCT for multiple myeloma and limited HSCT to selected patients [13, 14].
Q4. What was the powerful tool in CML?
Relapse risk was highest after T cell depletion in CML compared to other diseases, in contrast, donor lymphocyte infusion (DLI) proved to be the most powerful tool in CML.
Q5. What is the current recommendation of the ELN?
Current recommendations of professional organizations such as the ELN should consider integration of a quality management system into the treatment algorithm.
Q6. What is the role of the patient’s advocacy groups in the decision to end a transplant?
In order to arrive at such a policy, patients and patient’s advocacy groups need to be informed, cooperation has to be established between the local medical community and the transplant centers, professional organizations have to adapt recommendations within a quality management system and to collect and analyze the appropriate data.
Q7. What is the general consensus on HSCT?
The general consensus appears that allogeneic HSCT offers a reasonable outcome even in accelerated phase or blast crisis [52–57].
Q8. How much is the probability of survival after an allogeneic HSCT?
Hence,the general statement that the probability of survival after an allogeneic HSCT for CML at 5 years is 60 % is of limited value; it might range frommore than 90% to less than 5%.
Q9. What is the way to treat HSCT?
In case of early failure, HSCT could be considered rapidly for those with minimal transplant risks; drug treatment changed for those without this option.