Bone Marrow Transplantation in Nonmalignant Haematological Diseases: What Have We Learned about Thalassemia?
, Stefania Tringali 1, Giuseppe Sapienza 1, Roberto Bono 1, Rosario Di Maggio 2 and Aurelio Maggio 2
Farid Boulad
Round 1
Reviewer 1 Report
This short review summarizes the clinical literature on SCT in patients with transfusion-dependent Thalassemia (TDT), with a discussion about factors impacting these transplants, including patient age, stem cell source, the conditioning regimen, and alternative donors.
My comments:
1. All throughout the manuscript there are referrals to the Pesaro risk classification. It would be useful to add a small table depicting the Pesaro risk classes.
2. Line 50: The sentence "Major achievements after bone marrow transplantation in TDT in recent years." Is out of context. Is it a title? What are these major achievements?
3. Line 51: The sentence "The milestones in the field of allo-SCT in TDT can be summarized as follows:" is also out of context. What are the milestones? The sentence continues with a list of factors impacting outcomes.
4. Line 104: Did you mean CD3 cell counts? CD34 cell counts are not more than 1 log higher in PBSC compared to BM.
5. Lines 131-194: In the discussion about reduced toxicity conditioning regimens in TDT the aspect of mixed chimerism is not mentioned. Is mixed chimerism observed more in treosulfan-based transplants? What are the consequences of stable mixed chimerism in TDT? What level of chimerism is acceptable in these patients? It would be interesting to elaborate on this topic, especially in the context of reduced toxicity regimens.
6. The topic of gene therapy in TDT should be addressed.
Author Response
- All throughout the manuscript there are referrals to the Pesaro risk classification. It would be useful to add a small table depicting the Pesaro risk classes.
Done (Table 1)
- Line 50: The sentence "Major achievements after bone marrow transplantation in TDT in recent years." Is out of context. Is it a title? What are these major achievements? Line 51: The sentence "The milestones in the field of allo-SCT in TDT can be summarized as follows:" is also out of context. What are the milestones? The sentence continues with a list of factors impacting outcomes.
We agree with the reviewer and the sentences were modified (in yellow in the text)
- Line 104: Did you mean CD3 cell counts? CD34 cell counts are not more than 1 log higher in PBSC compared to BM.
Of course, we intended to report the higher number of CD34+ cells in PBSC compared to BM: At least 1 log was deleted. Thank you.
- Lines 131-194: In the discussion about reduced toxicity conditioning regimens in TDT the aspect of mixed chimerism is not mentioned. Is mixed chimerism observed more in treosulfan-based transplants? What are the consequences of stable mixed chimerism in TDT? What level of chimerism is acceptable in these patients? It would be interesting to elaborate on this topic, especially in the context of reduced toxicity regimens.
Thank you for this suggestion. We add a paragraph in page 6 (in yellow)
- The topic of gene therapy in TDT should be addressed
We add only one sentence in the conclusion because we think that more extensive on this topic could be out of the main topic of this review.
Reviewer 2 Report
Overall good review.
Not sure after reading this what the bottom line is.
Would rather have some final specific treatment recommendations
Would recommend making an algorithm.
< X years old + matched sib + Pesaro 1 -> Allo BMT
< X years old + NO matched sib + Pesaro 1 -> ?
< X years old + matched sib + Pesaro >1 -> ?
Y-Z years old …
> Z years old …
Including the other options: MUD transplant, Haplo MM transplant and Gene therapy
Comments for author File: 
Comments.docx
Author Response
Not sure after reading this what the bottom line is.
Would rather have some final specific treatment recommendations
Would recommend making an algorithm.
< X years old + matched sib + Pesaro 1 -> Allo BMT
< X years old + NO matched sib + Pesaro 1 -> ?
< X years old + matched sib + Pesaro >1 -> ?
Y-Z years old …
> Z years old …
Including the other options: MUD transplant, Haplo MM transplant and Gene therapy
I’m sorry for this comment, but of course I respect it. I agree with the Reviewer that this is not a new topic and many other have been published from more expert Authors.
It should be very interesting to answer with an algorithm and include in the paper suggestions and personal point of view on treatment recommendations. However, this is a simple revision of recent literature on the topic, trying to summarize main evidences.
In our hospital, located in Palermo, Sicily where most of thalassemic patients are resident, we are launching an allogeneic program for TDT. Our choice is to transplant “old” patients (more than 16 years), using treosulfano-based conditioning regimen whatever the donor, and regular GVHD prophylaxis with ATG, CSA and MTX for HLAid sib and matched UD, and PTCY + CSA + MMF for haplo and mMUD. Stem cell source is of preference bone marrow.
Round 2
Reviewer 1 Report
My comments are fully addressed.
To further improve the manuscript, I suggest English editing, especially in the newly added sections.
