Canterbury DHB

Acute Myeloid Leukaemia

For a general view of this topic, see Cornlissen and Lowenberg, ASH EPB, 2005.

Further reading:

• Vyas, P., et al. (2015). "Allogeneic hematopoietic cell transplantation for acute myeloid leukemia." Biol Blood Marrow Transplant 21(1): 8-15.
• Hubel, K., et al. (2011). "Allogeneic stem cell transplant in adult patients with acute myelogenous leukemia: a systematic analysis of international guidelines and recommendations." Leuk Lymphoma 52(3): 444-457.
• Oliansky, D. M., et al. (2008). "The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myelogenous leukemia in adults: an evidence-based review." Biol Blood Marrow Transplant 14(2): 137-180.

Allogeneic SCT in First Remission

Which young adults should receive allogeneic HCT in CR1?

For patients enrolled in a clinical trial, e.g. AML19 , it is recommended that patients follow the protocol and if a deviation is planned this is discussed with the trial organizers.

In patients with high risk AML survival after conventional chemotherapy is <20%. After allogeneic transplantation OS is 34-42% with comparable outcomes after MUD and MSD (Gupta, Tallman et al. 2010). In addition patients with normal cytogenetics in the intermediate risk group have 50% relapse risk with only a small chance of obtaining CR2 and also benefit from transplantation. Meta-analysis confirmed allogeneic SCT has significant RFS and overall survival benefit for intermediate- and poor-risk AML but not for good-risk AML in first complete remission (Koreth, Schlenk et al. 2009).

The NCCN and ASBMT both recommend [myeloablative] allogeneic SCT for patients with poor risk AML in CR1 up to the age of 55 yrs (Oliansky, Appelbaum et al. 2008). They recommend chemotherapy only for patients with good risk AML in CR1 and find insufficient evidence to recommend alloSCT in intermediate risk patients although it is described as “a reasonable approach”. There is insufficient evidence to recommend RIC over chemo in >55 year old outside of a clinical trial.

Allogeneic SCT is not recommended for good risk patients:

• AML with t(8;21), t(15;17) or inv(16) in CR1
• AML with normal cytogenetics, NPM1+, FLT3-ITD negative
• AML with normal cytogenetics, CEBPA mutation (double)

Allogeneic SCT may be recommended for fit patients with:

• AML intermediate or high risk cytogenetics, <55-60yrs (MRD, MUD)
• AML with normal cytogenetics, <55-60 yrs (MRD, MUD)

Allogeneic SCT is performed within a clinical trial for

• AML intermediate or high risk cytogenetics, >55yrs (MRD or MUD) in Swedish RIC study
• AML high risk in AML17 trial

Note: Autologous SCT for AML is no longer being performed in Christchurch outside of clinical trials.

Which older adults should receive allogeneic HCT in CR1?

Biological age is more important than chronological age in patients aged >60 years. All patients should be considered based on individual circumstances, however certain rules of thumb can be applied.

Older patients aged 60 to 75 years who should NOT receive HSCT:

• Poor PS (<80% or ECOG >1)
• Higher HCT-CI
• Active infection
• Active disease
• CBF or other favorable mutations
• CR2 and beyond

SCT in Second or Subsequent Remissions

Several international transplant groups have published guidelines that were recently analysed by Hubel at al (Hubel, Weingart et al. 2011). The EBMT, ASBMTR, BCSH and ESMO groups (Milligan, Grimwade et al. 2006; Oliansky, Appelbaum et al. 2008; Fey and Dreyling 2009; Ljungman, Bregni et al. 2010) recommend allogeneic SCT for all patients in CR2 with an available donor.

Key points to consider are:

• Achievement of CR2 is heavily dependent on CR1 >12 months (see ref 9)
• The European Prognostic Index stratifies patients by age, CR1 duration, previous allograft and unfavourable karotype at diagnosis with 5-yr OS of 46% (low risk), 12% (int) and 6% (poor) (Breems, Van Putten et al. 2005)
• The GOELAMS score uses unfavourable karyotype at diagnosis, FT3-ITD, and CR1 duration (Chevallier, Labopin et al. 2010)
• Salvage chemotherapy is palliative unless the aim is allogeneic SCT
• No salvage regimen has proved superior to another. FLAG is often used and CRs were achieved in non-randomised studies. No benefit was seen in a RCT [see ref 20]
• Few patients will reach allogeneic SCT due to refractory disease or lack of a donor.
• Although most patients will receive RIC this approach has not been well validated and the long time to establish a GVL will increase the chances of relapse.

Recommended reading:

• Szer, J. (2012). "The prevalent predicament of relapsed acute myeloid leukemia." Hematology Am Soc Hematol Educ Program 2012: 43-48.
• Hubel, K., et al. (2011). "Allogeneic stem cell transplant in adult patients with acute myelogenous leukemia: a systematic analysis of international guidelines and recommendations." Leuk Lymphoma 52(3): 444-457.

Prognostic scores in relapsed AML

Two year outcome: 0 points (good): OS 58%, EFS 45%; 1 point (intermediate): OS 37%, EFS 31%; 2 or 3 points (poor): OS 12%, EFS 12%.

One-year/5-year outcome: 0-6 points (good) OS 70%/46%; 7-9 points (intermediate) OS 49%/18%; 10-14 points (poor) OS 16%/4%.

Topic Code: 8145