We have a patient with relapsed acute myeloid leukemia (AML) after a myeloablative (Busulfan/Fludarabine) HSCT, and our plan is to take her into a 2nd HSCT. Can we take her to a 2nd myeloablative HSCT or it would be better to perform a reduced intensity HSCT due to increased risk of transplant-related toxicities?
As always, in those cases decision depends.
Aggressive relapse?
Same donor?
Time issue? Recipients weakness?
In some cases with aggressive relapse considering a mismatch was helpful (e.g. matched sibling vs. haplo).
Dr. Fischer,
My patient has 10% blasts in the bone marrow. Her performance status is excellent, KPS 80%. We are planning to take her to a haploidentical allogeneic transplant from her father.
I would ask those Qs: -What is the interval from SCT to relapse?
-How much Busulfan she received?
-Did you reinduce her now and which treatment?
-any molecular marker or cytogenetic that makes her eligible for a clinical trial now to deepen her response?
-What stem cells source and T-cell depletion strategy would you use?
-any plan for maintenance after SCT if not in CR at transplant.
Mostly some reduced regimes are used because of the fear of cummulative toxicity (as Antonio also stated). There was an education about 2nd tpx at ASH: http://asheducationbook.hematologylibrary.org/content/2009/1/414.long
Some German experience: http://www.karger.com/Article/Abstract/253025
Antonio,
The patient relapsed about 10 months after her first allo. She received myeloablative dose of Busulfan (16 doses over 4 days). After relapse she had about 20% blasts in the bone marrow, then she received Cytarabine 2000 mg/m2, every 12 hour, D1, D3 and D5. The blast percentage in the bone marrow went down to 10%. Her AML has normal cytogenetics, and it is negative for FLT3 and NPM1. For her first allo we used peripheral blood stem cells. She received ATG as part of her conditioning since she got a MUD Allo. So far we do not have any plan for maintenance after her 2nd allo.
in patients relapsing post 12 months from t depleted myeloablative allograft we have done t replete reduced intensity allograft with flu/ cyclo conditioning with methotrexate and ciclosporin as gvhd prophylaxis. Our experience was presented as a poster at ebmt.
It would be ideal to be in CR at transplant, as the outcome of patient undergoing second transplant is already inferior to first transplant.
Sometime mostly depend on patient choice also, whether to continue treatment and/or second SCT or hospice care.
http://www.nextavenue.org/blog/atul-gawande%E2%80%99s-5-questions-ask-life%E2%80%99s-end
To deepen the response if wanted, clofarabine for example could be a second induction treatment potentially able to re-induce patients in CR. Enrolling in a clinical trial if available would be good, as well.
As conditioning, one possibility could be to use a different regimen, we published about a retrospective experience with fludarabine melphalan and post-Cy in haplo-SCT, and of course for patients in CR1/CR2 the results were better as compared with patients not in CR.
If patients are not in CR at SCT , it would be good to consider maintenance Vidaza.
Or if not in CR post-SCT, to consider a clinical trial if available,.
http://www.nextavenue.org/blog/atul-gawande%E2%80%99s-5-questions-ask-life%E2%80%99s-end
In children without major organ dysfunction we would in general go for a second allo with such a relatively late relapse providing the patient is chemosensitive (ie at least obtains a partial remission) on reinduction chemo. As pointed out before, results are better if the patients enter CR. However, given that AML is so aggressive, the time frame is often short and the risk of the emergence of therapy resistance is imminent during reinduction chemo. Thus you don't have time to try too many different treatment options and may have to settle for a PR.
To achieve cure with the second transplant many believe that it is necessary to obtain a better GvL effect than following the first transplant. This makes haplo a good choice with careful monitoring of immunosuppressive therapy afterwards. I enclose an article which is a few years old but is comprehensive. The conditioning and immunomodulatory regimens in haplo SCT are however continuously evolving.
Apart from immunomodulation after transplant I am not aware of any effective "maintenence therapy" following transplant
Very difficult case. As others have pointed out and you surely know, the probability of achieving a cure of the AML are low, because this is an early or "near" early relapse. I assume the patient was transplanted in 1st CR.
I think you should deepen the quality of your response, 10% blasts is farily high, and you would risk a graft failure or no response at all. Ara C treatment alone most probably wont be able to achieve a remissioin. As Dr Stasi points out, clofarabine could be helpful coupled with ara C.
Regarding the donor for the 2nd transplant, it would not be advisable to choose the same donor, so an haplo could be a good strategy to acquire GVL mechanisms that haven't worked wit the first donor.
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