Haploidentical Unmanipulated G-CSF-Primed Peripheral Blood Stem Cell Transplantation for Patients with High-Risk Hematologic Malignancies

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.

 

Table 1. 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)

 

Figure 1. 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.

Figure 2. Disease-free survival according to disease status.