SCT Question 13

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Question 13

A 43-year-old lady with Ph+ ALL is now pancytopenic day 240 post PBSC transplant from her HLA matched sister after CY/TBI prep, and ATG/CsA/MTX for GVHD ppx. She was in CR1 at the time of transplant with initial therapy with HCVAD+TKI. She is now on dasatinib maintenance. There has been no GVHD. The patient is asymptomatic except for new onset fatigue since her clinic visit two weeks ago. Counts are, WBC 2.0 K/microL, PL 40 K/microL and Hgb 9 G/dL, ANC 0.3, AMC 0.2, ALC 1.5. BM shows no evidence of disease and is 60% cellular, diminished myelopoiesis is seen, dyspoeitic changes are seen. Karyotype is 46, XX, -7, +8, t(5:17) [8]/46, XX [12]. BM chimerism by amplification of STR shows 60% donor DNA in unfractionated bone marrow, 20% donor derived CD11+ cells and 100% donor derived CD3+ cells.

What is the best treatment plan at this time.

1. Observe with repeat CBC in two weeks

2. Change TKI to Ponatinib

3. Urgent donor lymphocyte infusion from same donor

4. Second transplant from a HLA matched unrelated donor

5. Commence azacitidine and sequential escalating dose DLI from same donor.


This patient with Ph+ ALL has now developed secondary MDS in her native marrow, presenting with pancytopenia and a complex karyotype, with predominantly recipient chimerism in her granulocytes. Typically, these patients are fully donor chimeric to begin with and as the secondary MDS clone begins to grow, donor marrow is suppressed. There is no evidence of Ph+ ALL. Her donor T cells are fully tolerized to this recipient clone, and there was no GVHD. Likely due to ATG being a part of her therapy. Ponatinib will be ineffective; she is severely neutropenic therefore therapy should be commenced as soon as possible. DLI alone will be ineffective. Induction therapy is often effective in patients with frank AML but is poorly tolerated. AZA DLI regimen developed by Schroeder et al is effective. in patients wit hrelatively low disease burden, another reasoon to commence therapy sooner than later.


Medicine and Health Sciences


Department of Medicine

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