We asked, and you answered! Here are the responses from this month’s “You Make the Call” question on whether or not you would proceed with a 7/8 matched unrelated donor alloHCT in a patient with severe acquired aplastic anemia?
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I would suggest a young mismatched unrelated donor, provided the patient does not have human leukocyte antigen (HLA) antibodies against the mismatched alleles.
For conditioning, I would rather give an alkylator- based protocol suitable for this age group. One possibility is two doses of fludarabine (30mg/m2), one or two doses of thiotepa (5mg/kg), and one dose of melphalan (110mg/m2), or three doses of teosulfan (10gm/m2) to avoid toxicity and the risk of graft rejection.
For graft-versus-host disease prophylaxis, I would give post-transplant cyclophosphamide (PT-CY) and then a calcineurin inhibitor plus mycophenolic acid.
Regarding an unrelated donor for the graft, we now prefer to use peripheral blood stem cells instead of bone marrow because of better graft function, though for haploidentical or mismatched sibling donors, bone marrow works fine with PT-CY.
Lastly, be sure to keep ferritin levels low with chelators before transplant.
Jürgen Finke, MD
Freiburg, Germany
I would proceed with a young mismatched unrelated donor.
Anastasia Skandalis, MD
Athens, Greece
I would not use a 7/8 mismatched unrelated donor for this semi-stable patient because the risk outweighs the benefit. I would rather attempt a second course of hATG or switch to rATG, as there was initial response, and try to prolong eltrombopag treatment with cyclosporine post-ATG.
This route places the least risk on the patient.
Deborah Vaz-Van der Riet, MBBCh, MMed
Hatfield, South Africa
Because the patient is clinically fit, I would opt for a matched unrelated donor as rATG will be used in conditioning rather than retreat with rATG. A 7/8 mismatched donor is fine, and chances of graft failure are minimal.
Shad Ahmed, MD, MBBS
Islamabad, Pakistan
This is a difficult decision. I would require more information before making a final recommendation. How small is the patient’s PNH clone? Is it growing? If yes, PNH might rescue the patient from aplastic anemia.
Lucio Luzzatto, MD
Florence, Italy
Yes, I would consider a transplant for this patient after ATG, cyclosporin, and eltrombopag therapy has failed. I would choose reduced-intensity conditioning with fludarabine, cyclophosphamide, and ATG, plus 4 Gy of total body irradiation and PT-CY, according to our haploidentical protocol. I would administer 30 mg/m2 of fludarabine daily for five days from day eight to day four; 14.5 mg/kg of cyclophosphamide on days eight and seven; 0.5 mg/kg, 2 mg/kg, and 2 mg/kg of ATG on days three, two, and one; and PT-CY with reduced dosage to 35 mg/kg per day for two days on days three and four post-transplant. I would also give cyclosporin or tacrolimus every 12 hours plus 750 mg to 1 gm of mycophenolate mofetil three times daily.
Tran-Der Tan, MD
Taipei City, Taiwan
I would give the patient rATG.
Troy H. Guthrie, Jr., MD
Jacksonville, Florida
I would first request panel-reactive (anti-donor) antibodies. If results are negative or slightly positive, I would proceed with an alloHCT.
If the patient has children, I would proceed with a haploidentical HCT from her children after HLA typing.
If not, I would go for 7/8 HLA-matched unrelated donor. Irrespective of donor selection, I would use bone marrow as the graft source along with PT-CY, in addition to conditioning with the ATG, fludarabine, and 2 Gy of total body irradiation.
Tugrul Elverdi, MD
Istanbul, Turkey
