Table 1.
Outcomes of Haplo-HCT with PTCy-Based Approaches.
| Author and year | Graft source [36] | Conditioning regimen [36] | N/age range (y) [36] | OS (%) (n) [36] | GvHD (%) (n) [36] | Engraftment (%) (n) [36] | Sickle cell-related and transplant outcomes [36] |
|---|---|---|---|---|---|---|---|
| Bolanos-Meade et al. [20] 2012 | G-BM (3), BM (11) | Nonmyeloablative ATG (12 patients), fludarabine, cyclophosphamide, 200-cGy total body irradiation GvHD prophylaxis: PTCy, FK, sirolimus, MMF |
14/15–42 | 100 (14/14) at 7.5–66 mo | 0 (0/14) acute GvHD 0% (0/14) chronic GvHD |
57 (8/14) | 50% (7/14) alive and without sickle cell-related symptoms No new strokes, acute chest syndrome, priapism Infections Three CMV reactivation, one EBV reactivation, one with RSV upper respiratory infection, and mycobacterium lung infection |
| Fitzhugh et al. [26] 2017 | PBSC | Nonmyeloablative alemtuzumab, 400-cGy total body irradiation GvHD prophylaxis: PTCy, sirolimus |
12/20–56 | 92 (11/12) |
8 (1/8) acute GvHD 8 (1/8) chronic GvHD |
70 |
No SCD-related issues, no sinusoidal obstruction syndrome Two patients with graft rejection developed high-grade myelodysplastic syndrome with fibrosis One patient with pulmonary hypertension and heart failure (died) One died from infection postsurgery 50% (6/12) alive and without sickle cell disease-associated symptoms Infections Four CMV reactivation, one CMV colitis, one disseminated adenovirus, three maintained chronic EBV viremia, one EBV-PTLD, three were treated for presumed fungal pulmonary nodules, and 15 bacteremia |
| Wiebking et al. [28] 2017 | BM | Myeloablative alemtuzumab, fludarabine, treosulfan, thiotepa, cyclophosphamide GvHD prophylaxis – PTCy, tacrolimus MMF |
3/8.5–20.3 | 100 (3/3) at 11–30 mo | 33 (1/3) Grades II–IV acute GvHD No chronic GvHD |
100 (3/3) | No central nervous system toxicity Infections Two CMV reactivation, one VZV reactivation |
| Pawlowska et al. [29] 2018 | BM (3), PBSC (1) | Pretransplant immunosuppression (fludarabine and dexamethasone) for two courses Nonmyeloablative ATG, busulfan, fludarabine GvHD prophylaxis: PTCy, tacrolimus, sirolimus and ruxolitinib (two patients), MMF |
4/13–23 | 100 (4/4) at range 5–11 mo | 25 (1/4) acute GvHD 75% (3/4) chronic GvHD |
100 (4/4) | Two patients had antibody management protocol (for high donor-specific anti-HLA antibodies) One patient with persistent opioid dependence Infections Three HHV-6 viremia and one CMV viremia |
| Saraf et al. [27] 2018 PTCy |
PBSC | Nonmyeloablative ATG, fludarabine, cyclophosphamide, 300-cGy total body irradiation GvHD prophylaxis: PTCy, MMF, sirolimus |
8/20–38 | 88 (7/8) 63 (5/8) EFS |
25 (2/8) acute GvHD 13 (1/8) chronic GvHD |
88 |
Infections Oral HSV-1, Escherichia coli urinary tract infection, enterococcus urinary tract infection, coronavirus, influenza, three CMV reactivation |
| de la Fuente et al. [30] 2018 PTCy |
BM | Nonmyeloablative ATG, fludarabine, cyclophosphamide, 200-cGy total body irradiation (all), and thiotepa (15 patients) GvHD prophylaxis: PTCy, MMF, sirolimus |
18/12.1–26 | 100 (16/16) | 13 (2/16) Grades III–IV acute GvHD 6 (1/16) limited chronic GvHD |
83 (15/18) | One case of sinusoidal obstruction syndrome Two posterior reversible encephalopathy syndrome One new infarct (patient who did not engraft) Suspected MMF-induced gastritis, ulcer with bleeding, typhlitis Infections Six with EBV reactivation (no PTLD), three with CMV reactivation, one adenovirus respiratory infection, one BK cystitis, two cases of oral HSV infection, and two HHV-6 viremia (1 with HHV-6 encephalopathy) |
| Bolanos-Meade et al. [31] 2019 | BM | Nonmyeloablative ATG, fludarabine, cyclophosphamide, 400-cGy total body irradiation GvHD prophylaxis: PTCy, MMF, sirolimus |
17/6–31 (median age 16 years | 100 (17/17) | 29 (5/17) Grades II–IV acute GvHD 18 (3/17) chronic GvHD |
94 (16/17) | Twelve patients with sickle cell disease and five with beta-thalassemia major Donors found for all 17 consecutive patients 76% (13/17) achieved full donor chimerism 18% (3/17) with mixed donor chimerism 18% (3/17) remained on immunosuppression 6% (1/16) of engrafted patient transfusion dependent |
Note: We thank the editors for careful review of our article. Table 1 shares similarities with our aforementioned published work, namely Patel et al. [36]. ATG = antithymocyte globulin; BM = bone marrow; cGy = centigray; CMV = cytomegalovirus; EBV = Epstein-Barr virus; EFS = event-free survival; G-BM = granulocyte colony-stimulating factor primed bone marrow; GvHD = graft versus host disease; Haplo = haploidentical; HCT = hematopoietic cell transplant; HLA = human leukocyte antigen; MMF = mycophenolate mofetil; OS = overall survival; PBSC = peripheral blood stem cell; PTCy = post-transplant cyclophosphamide; PTIS = pretransplant immune suppression; PTLD = post-transplant lymphoproliferative disorder; RIC = reduced intensity conditioning.