Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective, even curative, treatment for patients with high-risk hematologic malignancies. Transplantation from haploidentical donors (haplo-HCT) has been applied for the treatment of hematologic malignancies within the past 2 decades. Bone marrow (BM), G-CSF-primed peripheral blood stem cells (PBSCs), G-CSF-primed BM (G-BM) or the combination of PBSCs and G-BM can serve as stem cell sources for allo-HCT. The optimal source of stem cells in cases of haplo-HCT without ex vivo TCD under myeloablative conditioning is not yet clear. Therefore, we initiated a study of unmanipulated haplo-HCT from PBSCs (haplo-PBSCT) for the treatment of high-risk hematologic malignancies. In this report, we analyzed 89 adult patients who received consecutive haplo-PBSCT to evaluate the efficacy and safety of this transplantation procedure.
PATIENTS AND METHODS
Eighty-nine patients received consecutive haploidentical allo-PBSCT between July, 2007 ¨C June, 2014 at the Chinese PLA General Hospital, Beijing, China (Table 1). PBSCs were freshly isolated and infused into the recipients. The conditioning regimen consisted of Bu (3.2 mg.kg-1.d-1 intravenously, days -10 to -8), Carmustine, 250 mg.m-2, day -5), cytarabine (4 g.m-2.d-1, days -7 to -6), cyclophosphamide (60mg kg-1.d-1, days -4 to -3), and ATG (Thymoglobuline, rabbit; 2.5 mg.kg-1.d-1, days -5 to -2). All transplant recipients received CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis.
"High-risk'' hematologic malignancies were defined as: 1) AL with the [t(9;22)(q34;q11)], Flt3-ITD mutation, mixed lineage leukemia genes and complex cytogenetics regardless of disease stage; 2) AML-CR1 after 3 or more cycles of induction, ALL-CR1 after 4 weeks of induction or AL-CR1 with positive MRD after 2 cycles of consolidation; 3) AL beyond CR2 or in non-remission (NR) regardless of cytogenetics, or CML beyond CP1; and 4) T cell lymphoblastic lymphoma in CR and T cell lymphoma resistant to chemotherapy or autologous transplantation. The endpoint of the last follow-up for all surviving patients was January 31, 2015.
RESULTS
Sustained myeloid engraftment with full donor chimerism was achieved in 89 patients (100%) at a median of 16 (10 - 26) days. Eighty patients (89.9%) achieved platelet recovery in a median of 28 (10 - 207) days. The occurrence of GVHD was showed in Fig 1.
The 3-year of cumulative incidence of transplant-related mortality was 23.4% ± 5.4%. Non-remission status prior to transplant was found to be significantly correlated with relapse (P = 0.006, odds ratio [OR] = 3.17), leukemia-free survival (P = 0.013, OR = 2.48) (Fig. 2) and overall survival (P = 0.03, OR = 2.27).
CONCLUSION
The results described rapid and complete neutrophil engraftment, a low incidence of grade 3-4 GVHD and promising survival in patients with high-risk hematologic malignancies. It demonstrated the reliability of G-CSF-primed PBSCs as a graft source in unmanipulated haplo-HCT under myeloablative conditioning.
Patient and donor characteristics
| Cases | % | |
|---|---|---|
| Gender, n (%) | ||
| Male | 69 | 77.5 |
| Age, y, median(range) | ||
| Patient | ||
| <46 y, n (%) | 28(6-59) | |
| Donor | ||
| >40 y, n (%) | 38(9-61) | |
| Hematologic malignancy, n (%) | ||
| AML | 51 | 57.3 |
| CR1 CR2* | 23 3 | |
| NR*/beyond CR2 | 23/1 | |
| ALL | 20 | 22.5 |
| CR1 CR2 | 10 7 | |
| NR | 3 | |
| CML | 5 | 5.6 |
| CP1* | 2 | |
| AP/CP2 | 1/2 | |
| Lymphoma | 13 | 14.6 |
| CR | 5 | |
| Resistant | 8 | |
| Donor/recipient relationship, n (%) | ||
| Parent | 47 | 52.8 |
| Sibling | 26 | 29.2 |
| Child | 12 | 13.5 |
| Lateral relative | 4 | 4.5 |
| No. of HLA antigens (A/B/DR) mismatched, n(%) | ||
| 1 | 18 | 20.2 |
| 2 | 25 | 28.1 |
| 3 | 46 | 51.7 |
| Second HCT | 9 | 10.1 |
| Graft: | ||
| MNC (108/kg) | 11.04 (5.64-36.46) | |
| CD34+ (106/kg) | 5.83 (2-23.73) |
| Cases | % | |
|---|---|---|
| Gender, n (%) | ||
| Male | 69 | 77.5 |
| Age, y, median(range) | ||
| Patient | ||
| <46 y, n (%) | 28(6-59) | |
| Donor | ||
| >40 y, n (%) | 38(9-61) | |
| Hematologic malignancy, n (%) | ||
| AML | 51 | 57.3 |
| CR1 CR2* | 23 3 | |
| NR*/beyond CR2 | 23/1 | |
| ALL | 20 | 22.5 |
| CR1 CR2 | 10 7 | |
| NR | 3 | |
| CML | 5 | 5.6 |
| CP1* | 2 | |
| AP/CP2 | 1/2 | |
| Lymphoma | 13 | 14.6 |
| CR | 5 | |
| Resistant | 8 | |
| Donor/recipient relationship, n (%) | ||
| Parent | 47 | 52.8 |
| Sibling | 26 | 29.2 |
| Child | 12 | 13.5 |
| Lateral relative | 4 | 4.5 |
| No. of HLA antigens (A/B/DR) mismatched, n(%) | ||
| 1 | 18 | 20.2 |
| 2 | 25 | 28.1 |
| 3 | 46 | 51.7 |
| Second HCT | 9 | 10.1 |
| Graft: | ||
| MNC (108/kg) | 11.04 (5.64-36.46) | |
| CD34+ (106/kg) | 5.83 (2-23.73) |
Acute and chronic GVHD. (A) CI (Cumulative Incidence) of grade 2-4 (continuous line) and grade 3-4 (dotted line) acute GVHD. (B) CI of total (continuous line) and moderate to severe (dotted line) chronic GVHD.
Acute and chronic GVHD. (A) CI (Cumulative Incidence) of grade 2-4 (continuous line) and grade 3-4 (dotted line) acute GVHD. (B) CI of total (continuous line) and moderate to severe (dotted line) chronic GVHD.
Disease-free survival according to disease status.
No relevant conflicts of interest to declare.
