The Role of Allogeneic Transplantation in Chronic Myeloid Leukemia in 2023: A Case-Based Concise Review
, Giuseppe Petruzzellis 1, Giulia Battaglia 1, Martina Pucillo 1, Marta Lisa Battista 1, Michela Cerno 1, Antonella Geromin 1, Gabriele Facchin 1, Umberto Pizzano 1, Daniela Damiani 1,2, Renato Fanin 1,2 and Francesca Patriarca 1,2,*
Peter Westerweel
Round 1
Reviewer 1 Report
Major comment:
1. The novel TKI asciminib is now available and is likely to impact the indication of allogeneic stem cell transplantation as treatment line. The impact of asciminib should be discussed in the manuscript: would asciminib currently be used as an alternative to allo-SCT in any of the cases?
2. For case 3: For a second line treatment, a BCR::ABL level 0,1-1% would generally be acceptable according to the ELN recommendations at the time. It is unclear why the authors concluded that a transplant was warranted with a patient in CCyR and a BCR::ABL1 0,1-1% (0.3%) after 12 months treatment. Was there a loss of previous deeper response or was (hemato)toxicity unacceptable?
line 11: (Abstract ) I suggest to remove the word “literally” to avoid hyperinflation of terminology
Line 59: “AP Phase” should be “AP” or “Accelerated Phase”
Line 66: the meaning of the term “TKI prophylaxis” is unclear.
Line 93: “die” should be “day”
Line 183 “metilprednisolone” should read “methylprednisolone"
Author Response
Major comment:
- The novel TKI asciminib is now available and is likely to impact the indication of allogeneic stem cell transplantation as treatment line. The impact of asciminib should be discussed in the manuscript: would asciminib currently be used as an alternative to allo-SCT in any of the cases?
We agree that the advent of asciminib adds a valuable option for CML patients resistant or intolerant to multiple TKIs. Probably, in the “real world”, asciminib will be the alternative to ponatinib in patients failing a 2G-TKI, taking advantage of a (still supposed) safety on the cardiovascular side. Nonetheless, we feel that allogeneic transplant will remain an option in selected CML patients.
A brief discussion on the possible role of asciminib in CML management has been added to the manuscript.
- For case 3: For a second line treatment, a BCR::ABL level 0,1-1% would generally be acceptable according to the ELN recommendations at the time. It is unclear why the authors concluded that a transplant was warranted with a patient in CCyR and a BCR::ABL1 0,1-1% (0.3%) after 12 months treatment. Was there a loss of previous deeper response or was (hemato)toxicity unacceptable?
We agree with the reviewer that, in case #3, indication to allogeneic HCT could be debatable. We considered the high-risk features at diagnosis, the poor response to first line nilotinib and the hematologic toxicity to both nilotinib and second line ponatinib that forced to reduce ponatinib therapy. In the end, the MR2 response after 12 months of ponatinib was felt to be not so satisfactory and the identification of a full-matched donor and patient’s will prompted us to proceed with transplant.
Comments on the Quality of English Language
line 11: (Abstract) I suggest to remove the word “literally” to avoid hyperinflation of terminology
The word has been removed.
Line 59: “AP Phase” should be “AP” or “Accelerated Phase.”
This has been corrected.
Line 66: the meaning of the term “TKI prophylaxis” is unclear.
The term refers to a prophylactic use of TKI after transplant irrespectively of molecular response based on the evaluation of relapse risk after transplant. Conversely, the pre-emptive strategy means the use of TKI based on the evidence of molecular relapse of CML after HCT.
Line 93: “die” should be “day.”
Corrected.
Line 183 “metilprednisolone” should read “methylprednisolone."
Corrected.
Reviewer 2 Report
A case based review is interesting but not unique. There have been a number of reviews of this topic over the last few years including ASH Education sessions.
The report is well written, but in reality, does not really add much to the literature that is out there.
I know this journal issue is a tribute to a giant in cml and a long standing colleague of mine, but this manuscript is not likely to be quoted.
Author Response
We agree that the topic of allogeneic HCT in CML is not very original but, as stated, it is still debated, and several recent papers reflected on the pros and cons for HCT in this setting. We feel that a case-based review could reflect challenges posed to both the “CML doctors” and the transplant teams by real-world patients.
More, as correctly underlined by the reviewer, the Journal Memorial Issue is intended to be a tribute of the Head of the authors’ institution and the mentor of most of them.
Reviewer 3 Report
The paper of Tribelli et al. describes 3 case reports of younger patients with CML with either suboptimal response to TKI treatment or toxicities leading to allogenic hematopoietic stem cell transplantation (HSCT). A discussion of the literature is provided.
Overall the paper is well written and ,even if not very original, contributes to the eternal pros and cons for HSCT in this setting.
The main issue is the too positive view of HSCT and should be stressed in the discussion by the approval of asciminib recently and the low risk of progression of MR2 patients continuing TKI treatment.
Author Response
We thank the reviewer for his/her appreciation of our work.
As suggested also by another reviewer, a brief discussion on the possible role of asciminib in CML patients resistant or intolerant to multiple TKIs has been added to the manuscript. However, we fell that, despite the more-than-welcomed approval of novel agents, HCT will probably remain an indication for selected CML patients.
Round 2
Reviewer 1 Report
I have no further comments
I have no further comments
Reviewer 2 Report
none
