J Korean Med Sci.  2021 Jun;36(23):e151. 10.3346/jkms.2021.36.e151.

Incidence, Management, and Prognosis of Graft Failure and Autologous Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

• Park JH
• Lee JH
• Lee JH
• Park HS
• Choi EJ
• Kang YA
• Kang H
• Woo JM
• Lee YS
• Jeon M
• Lee KH

• KMID: 2516676
• DOI: http://doi.org/10.3346/jkms.2021.36.e151

Abstract

Background
This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR).
Methods
We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000– September 2017) at our center.
Results
Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse.
Conclusion
Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.

Keyword

Autologous Reconstitution; Primary Graft Failure; Secondary Graft Failure; Reduced-intensity Conditioning

Figure

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  Fig. 1 Selection process of patients with graft failure.AMC = Asan Medical Center, HCT = hematopoietic stem cell transplantation, ANC = absolute neutrophil count.aForty-nine patients died within 1 month after HCT without achieving ANC greater than 1,000/μL. Causes of death in these patients were sepsis/organ failure (n = 23), progression of underlying malignancy (n = 23), cerebral hemorrhage (n = 2), and encephalopathy (n = 1).

• 

  Fig. 2 Ten-year cumulative incidence of secondary graft failure. (A) Patient age group and cumulative incidence of secondary graft failure (P = 0.042). (B) Pretransplant diagnosis and cumulative incidence of secondary graft failure (P < 0.001). (C) Conditioning regimen and cumulative incidence of secondary graft failure (P < 0.001). Note that most of the Cy-flu-ATG recipients were diagnosed with severe aplastic anemia. (D) Total nuclear cell dose and cumulative incidence of secondary graft failure (P = 0.049).HCT = hematopoietic stem cell transplantation, SAA = severe aplastic anemia, MDS = myelodysplastic syndrome, MPD = myeloproliferative disorder, AML = acute myeloid leukemia, CML = chronic myeloid leukemia, ALL = acute lymphoblastic leukemia, NHL = non-Hodgkin lymphoma, HL = Hodgkin lymphoma, MM = multiple myeloma, ATG = antithymocyte globulin.

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  Fig. 3 K-M survival rate in secondary graft failure. (A) K-M survival rate in patients with severe aplastic anemia and malignant disease (P = 0.049). (B) K-M survival rate in patients with standard risk status compared with those in high-risk status at time of HCT (P < 0.001). (C) Performance status and K-M survival rate (P < 0.001). (D) K-M survival rate compared between conditioning regimens. Patients experienced secondary graft failure after myeloablative conditioning regimen had shorter survival (P = 0.001).CML = chronic myeloid leukemia, SAA = severe aplastic anemia, AML = acute myeloid leukemia, ALL = acute lymphoblastic leukemia, MDS = myelodysplastic syndrome, MPD = myeloproliferative disorder, ATG = antithymocyte globulin, K-M = Kaplan-Meier.

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