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Summary: To investigate the clinical characteristics and risk factors of specific human leukocyte antigen loss (HLA loss) in relapsed acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) patients after allogeneic haematopoietic stem cell transplantation (allo‐HSCT), and compare the responses of patients with HLA loss relapse with those without HLA loss (non‐HLA loss) to different treatment regimens. Clinical data of traceable patients with AML/MDS after myeloablative allo‐HSCT in our centre between January 2010 and June 2021, who experienced disease relapse after the transplantation, were collected. The patients were divided into the HLA loss relapse group and the non‐HLA loss relapsed group based on HLA loss gene test findings by next‐generation sequencing. The patients' median overall survival (OS) after the relapse were compared, and univariate and multivariate analyses were performed using the Kaplan–Meier survival curve and Cox proportional hazard model to explore the responses to different treatments after relapse. A total of 2359 patients were selected. Retrospective HLA gene loss gene detection was performed for the deoxyribonucleic acid in 179 relapsed patients, including 47 patients in the HLA loss group (27.2%), 126 patients in the non‐HLA loss group (72.8%) and 6 patients were excluded due to a lack of confirmed results. There was no significant statistical difference in the baseline characteristics of patients between the two groups, but as to transplantation‐related characteristics, the donor–recipient relationship and HLA mismatched loci were statistically different between the two groups (both p < 0.001). Multivariate Cox analysis showed that more HLA mismatched loci ≥3 (HR = 3.66; 95% CI: 1.61–8.31; p = 0.002), time (≤6 months) from HSCT to relapse (HR = 7.92; 95% CI: 3.35–18.74; p < 0.001) and donor chimerism (CD3) in bone marrow at relapse (HR = 1.02; 95% CI: 1.00–1.03; p = 0.036) were independent factors affecting HLA loss relapse. The ratio of negative conversion of FLT3‐ITD or CEBPA mutation was significantly lower in patients with post‐transplantation HLA loss relapse than in the non‐HLA loss group (0.0% vs. 45.5%, p = 0.003; 0.0% vs. 80.0%, p = 0.035), with none of the patients with FLT3‐ITD or CEBPA mutation turned negative in the HLA loss group. The number of gene mutations turned negative when relapse in the non‐HLA loss group was remarkably higher than that in the HLA loss group (p = 0.001). Using donor lymphocyte infusion (DLI) could not prolong OS for the HLA loss group (p = 0.42). Nevertheless, second transplantation had a significant positive impact on OS in the HLA loss group (p = 0.017), although only five patients in the HLA loss group underwent second transplantation. However, patients in the non‐HLA loss group using DLI had a relatively longer OS time than those without DLI (p = 0.017). Second transplantation could also prolong OS in the non‐HLA loss group, but the effect was not as significant as in the HLA loss group (p = 0.053). In summary, HLA loss detection is essential for patients with recurrence after transplantation, especially for those with more HLA mismatched loci and non‐sibling donor. Furthermore, the detection of HLA loss has a guiding role in choosing subsequent therapy when relapsed, as secondary transplantation is more suitable than DLI for those with HLA loss. [ABSTRACT FROM AUTHOR]

Aim: It is known that the prognosis of acute leukemia patients who relapse after the first allogeneic stem cell transplantation (ASCT) is dismal. Our goal was to assess the value of a second allogeneic stem cell transplant in acute leukemia patients who experienced post-transplant recurrence. Material and Methods: We retrospectively reviewed data from 29 patients with relapsing acute leukemia who underwent a second ASCT. Nineteen patients with acute myeloid leukemia and ten patients with acute lymphoblastic leukemia were included in the study. Results: Ten AML patients and 10 ALL patients were included in the study. Most patients (62%) were in remission before the second transplantation. The median time between the first and second ASCT was 11.9 months (3.1-42 months). Complete remission (CR) was achieved after the second ASCT in 21 (72%) patients, and 11 (52%) patients relapsed after the second ASCT. During this analysis, six patients (21%) were alive and in remission. Relapse of the disease was the leading cause of mortality. After the second ASCT, overall survival (OS) was 6.34 months, and leukemia-free survival (LFS) was 13.8 months. Conclusion: For patients with acute leukemia who relapsed after the first ASCT, a second ASCT is a good option and can keep patients alive. [ABSTRACT FROM AUTHOR]

Background: We retrospectively analyzed the application and clinical efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia patients who relapsed or had primary graft failure (PGF) after first transplantation. Methods: From 2007 to 2021, eight patients with acute leukemia who received second allo-HSCT in our hospital were collected, including 6 relapsed patients and 2 patients with PGF after the first HSCT. Results: All the patients received complete donor implantation after second transplantation. The median time of neutrophils and platelet implantation were 12 days (10 days - 13 days) and 23 days (12 days - 123 days). Two cases (25.0%) developed grade II aGVHD, and 4 cases (50.0%) developed cGVHD. Leukemia-free survival (LFS) and overall survival (OS) at 1 year both were 71.4% and at 3 years both were 28.6%. After a median follow-up of 1,556 days (range, 257 - 5,252 days), 3 of the patients (37.5%) survived and 5 (62.5%) died. One patient with NR before second transplantation, treated with a conditioning regime of CLAG-M bridging BuCy, has survived for more than 5 years (61 months). Relapse was the main death reason. Conclusions: Second allo-HSCT is an effective means to treat acute leukemia patients with relapsed and PGF after first transplantation. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the preferred treatment for children with high-risk hematologic malignancies, but post-allo-HSCT relapse has a poor prognosis and limited treatment options. We evaluated the feasibility, outcome, and risk factors influencing survival after T-cell-replete haploidentical HSCT with low-dose anti-thymocyte globulin (ATG) in 30 patients with post-allo-HSCT relapse of acute lymphoblastic leukemia and acute myeloid leukemia. Overall, 50% of the patients had complete remission (CR) before the second transplant and the overall survival (OS) rate was 52%. In surviving patients (median follow-up 614 days), Kaplan–Meier analysis revealed estimated 2-year leukemia-free survival and OS rates of 48.1% and 61.1%, respectively. Cumulative incidences of 2-year non-relapse mortality and relapse were 24.7% and 36.3%, respectively. Achieving CR before the second allo-HSCT was a predominant independent prognostic factor identified in the multivariate analysis, with a significantly improved 2-year OS rate of 86.7%. T-cell-replete haplo-HSCT with low-dose ATG for second allo-HSCT may benefit a selected patient population. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical efficacy and its influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT2) in acute myeloid leukemia (AML) patients who have relapsed after the first allogeneic transplantation. Methods Clinical data of 5 patients with refractory/relapsed AML who had relapsed after allo-HSCT in our medical center from January 2012 to October 2018 were collected in this study. After re-induction (CR2-MRD- was achieved in 3 cases, CR2-MRD+ in 1 case, and NR in 1 case) and myeloablative pretreatment, allo-HSCT2 was conducted to all of them. The clinical process and outcome of these cases were analyzed, and the possible effects of alleviation status, donor selection, pretreatment protocol of the allo-HSCT2 patients before transplantation on the complications, recurrence and death (RM), transplant-related mortality (TRM), and transplantation outcome were also investigated. Results Until the 5 patients were followed up to June 30, 2019, all of them achieved complete donor implantation. Three of them had no relapse within 17 months, and 1 patient developed acute graft versus host disease (aGVHD) grade Ⅰ and chronic graft versus host disease (cGVHD) as severe lung disease, and hence deceased due to respiratory failure in 20 months after the allo-HSCT2. No serious HSCT-related complications were observed in the other 4 patients. The patients with complete remission of allo-HSCT2 with a negative status of (minimal residual disease, MRD), proved to have a better prognosis. Second allo-HSCT did not increase TRM compared with one-time allo-HSCT. For the patients receiving allo-HSCT2, the GVL effect of haploid transplantation had no significant advantage against full-matched HSCT. Conclusion Allo-HSCT2 is an effective therapy for AML patients who relapsed after the first allo-HSCT.

Abstract Background Patients with relapsed/refractory acute myeloid leukemia after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, with a 2-year survival rate of 14%. The optimal treatment for these patients remains unclear. To treat these patients, we designed a new salvage regimen consisting of decitabine, cladribine, cytarabine, and granulocyte-stimulating factor (D-CLAG). Case presentation Here, we describe a case of acute monocytic leukemia with a complex karyotype in a 38-year-old female patient who relapsed after her first HSCT, which was performed using a matched sibling donor. The patient did not respond to standard induction chemotherapy and subsequently achieved complete remission with the D-CLAG regimen. No severe hematological or extramedullary toxicity was observed. Subsequently, the patient received a second D-CLAG regimen as a bridge therapy and directly underwent haploidentical related HSCT. Following HSCT, the marrow showed complete hematologic and cytogenetic remission. Currently, 1 year after transplantation, the patient’s general condition remains good. Conclusions This case suggests that the D-CLAG regimen can be an option for reinduction in relapsed refractory AML patients as a bridge to transplantation. Nevertheless, further research will be required in the future as this report describes only a single case.

Graft failure (GF) is a fatal complication of allogeneic stem cell transplantation, especially after haploidentical transplantation. The mortality of GF is nearly 100% without an effective salvage method. A second transplantation is usually necessary to save the patient's life. However, there is no standardized regimen, and the outcome is usually disappointing. We report on a prospective single-center study using a reduced-intensity conditioning regimen with different haploidentical donors (HIDs). Patients with GF after the first transplantation were enrolled in a prospective single-arm clinical trial (ClinicalTrials.Gov ID: NCT03717545) at the Peking University Institute of Hematology. The conditioning regimen consisted of fludarabine (30 mg/m2) (days−6 to−2) and cyclophosphamide (1,000 mg/m2/day) (days−5 to−4). Patients underwent a second transplant from a different HID using a granulocyte colony-stimulating factor primed bone marrow and peripheral blood stem cells. The primary outcome was neutrophil engraftment at day 28. The secondary outcomes included platelet engraftment at day 100, transplant-related mortality (TRM) at day 30, TRM at day 100, and overall survival (OS) at 1 year. From March 2018 to June 2020, 13 patients were enrolled in this clinical trial. Of the 13 patients, five had acute myeloid leukemia, five had acute lymphoblastic leukemia, two had myelodysplastic syndromes, and one had a non-Hodgkin lymphoma. The median age at first transplantation was 38 years (range, 8–55 years). As for the first transplantation, 11 patients underwent haploidentical transplantations and two underwent unrelated donor transplantations. At the time of GF, three patients had complete donor chimerism, five had mixed chimerism, and five had complete recipient chimerism. The median time from the first transplantation to the second transplantation was 49 (range 35–120) days. The medians of infused cell doses were as follows: mononuclear cells 7.93 (5.95–12.51) × 108/kg and CD34 + cells 2.28 (0.75–5.57) × 106/kg. All 13 patients achieved neutrophil engraftment after the second transplantation, with a median engraftment time of 11 (range 10–20) days after transplantation. The platelet engraftment rate on day 100 after transplantation was 76.9%. The TRMs at day 30, day 100, and 1-year were 0, 0, and 23.1%, respectively. The OS and disease-free survival at 1-year were 56.6 and 48.4%, respectively. For patients with GF after first transplantation, a second transplantation using a fludarabine/cyclophosphamide regimen from a different HID was a promising salvage option. Further investigation is needed to confirm the suitability of this method.

We examined outcomes of 51 pediatric patients with relapsed acute leukemia (AL) who underwent a second allogeneic hematopoietic stem cell transplantation (alloHSCT). After a median follow-up of 941 days (range, 69–2842 days), leukemia-free survival (LFS) and overall survival (OS) at 3 years were 26.6% and 25.6%, respectively. The nonrelapse mortality rate (NMR) and cumulative incidence of relapse (CIR) were 36.4% and 42.4%, respectively. The Cox regression analysis demonstrated that the risk factors at second transplantation for predicting limited LFS were active disease (hazard ratio (HR) = 5.1), reduced intensity conditioning (RIC) (HR = 5.0), matched unrelated donor (MUD) (HR = 3.4) and performance score <80 (HR = 3.2). Pediatric patients with AL who relapsed after their first alloHSCT may survive with a second alloHSCT. Disease status, conditioning intensity, donor type, and performance score at the second transplantation are the relevant risk factors. A score based on these factors may predict the results of the second transplantation. [ABSTRACT FROM AUTHOR]

Background: Despite advances in immunosuppressant medications, improvement in long-term survival for kidney transplant recipients has been more difficult to achieve. In fact, the number of patients with failing grafts who must either return to dialysis or undergo a second transplant is increasing. Second transplantation is associated with reduced mortality rates compared to remaining on dialysis after an initial graft loss. Nowadays, excellent ABO-incompatible kidney transplant outcomes have been achieved. However, there have been no reports on ABO-incompatible kidney transplantation as a second transplant. Patients and Methods: Three patients who received their graft from an ABO-incompatible living donor at our institution as a second transplant were enrolled in this study. We focused on immunosuppressive therapy for second ABO-incompatible kidney transplantation, donor-specific antibody status before the second transplant, patient and graft survivals, and complications. Results: All 3 patients successfully underwent ABO-incompatible kidney transplantation as a second transplant with a follow-up period of 141, 39, and 24 months. Patient and graft survival rates were 100%. Conclusions: ABO-incompatible kidney transplantation may be an acceptable treatment for patients who need a second renal replacement therapy after their initial graft failure. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed/refractory acute myeloid leukemia after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, with a 2-year survival rate of 14%. The optimal treatment for these patients remains unclear. To treat these patients, we designed a new salvage regimen consisting of decitabine, cladribine, cytarabine, and granulocyte-stimulating factor (D-CLAG).Case Presentation: Here, we describe a case of acute monocytic leukemia with a complex karyotype in a 38-year-old female patient who relapsed after her first HSCT, which was performed using a matched sibling donor. The patient did not respond to standard induction chemotherapy and subsequently achieved complete remission with the D-CLAG regimen. No severe hematological or extramedullary toxicity was observed. Subsequently, the patient received a second D-CLAG regimen as a bridge therapy and directly underwent haploidentical related HSCT. Following HSCT, the marrow showed complete hematologic and cytogenetic remission. Currently, 1 year after transplantation, the patient's general condition remains good.Conclusions: This case suggests that the D-CLAG regimen can be an option for reinduction in relapsed refractory AML patients as a bridge to transplantation. Nevertheless, further research will be required in the future as this report describes only a single case. [ABSTRACT FROM AUTHOR]

Objective Infections after a second hematopoietic stem cell transplantation (HSCT) occur commonly and are associated with high mortality. However, studies on bloodstream infection (BSI) after a second HSCT are lacking. We therefore evaluated the details of BSI after a second HSCT. Methods We retrospectively evaluated the incidence, etiology, risk factors, and outcomes of BSI after a second HSCT. Patients Fifty-two adult patients with hematological malignancies who underwent allogeneic HSCT, including cord blood transplantation (CBT; n=33), as the second transplantation were enrolled. The second transplantation was limited to allogeneic HSCT. Patients who underwent HSCT for graft failure were excluded. Results The median HSCT interval was 438 (range: 39-3,893) days. Overall, 31 (59.6%) patients received autologous HSCT as the first HSCT. The cumulative incidence of BSI was 40.4% at 100 days after the second HSCT, with Gram-positive bacteria accounting for the majority (30.8%) of pathogens. Overall, 92.0% of BSIs occurred during the pre-engraftment period, and Enterococcus faecium accounted for 29.6% of pathogens. On a multivariate analysis, CBT was most closely associated with pre-engraftment BSI after the second HSCT (hazard ratio: 3.43, 95% confidence interval: 1.05-11.23, p=0.042). The 1-year survival rate after the second HSCT was lower in patients with BSI than in patients without BSI (p=0.10). Conclusion BSI is common after a second HSCT, especially with CBT. During the pre-engraftment period, BSI caused by pathogens such as E. faecium should be anticipated and appropriately treated to improve transplant outcomes.

BKV-HC is a serious complication of allogeneic HSCT. To characterize the incidence, risk factors, and clinical outcomes of post-HSCT BKV-HC, we retrospectively analyzed 112 patients who underwent one or more allogeneic HSCTs at our hospital between 2001 and 2017. Twenty underwent second or third HSCT thereafter. Ten patients developed BKV- HC at a median of 30 days after HSCT. The 100-day cumulative incidences of grade 0-4 and grade 2-4 BKV- HC were 7.8% and 6.2%, respectively. HSCTs performed in 2011-2017 associated with significantly higher 100-day cumulative incidence of grade 2-4 BKV-HC (14.0%) than HSCTs performed in 2001-2010 (1.3%, P = 0.004). On multivariate analysis, second or third HSCT was the only independent significant risk factor for development of grade 2-4 BKV- HC (P = 0.015). Serial PCR monitoring of urine and blood BKV load did not predict BKV-HC. The recent increase in the incidence of BKV- HC may reflect recent innovations in transplant technologies that facilitate second or third HSCT, which are known to cause prolonged immune deficiency. If safe and effective treatment or prophylaxis becomes available, it could be used to target the high-risk patients for BKV-HC. [ABSTRACT FROM AUTHOR]

Summary: The impact of preemptive second kidney transplantation (2KT) on graft and patient survival is poorly established. The association between preemptive 2KT (p2KT, N = 93) and outcomes was estimated in a multicenter French cohort of 2KT (N = 1314) recipients using propensity score methods. During the follow‐up, there were 274 returns to dialysis and 134 deaths. p2KT was associated with lower death‐censored graft loss (HR = 0.39 [0.18–0.88], P = 0.024) and graft failure from any cause including death (HR = 0.42 [0.22–0.80], P = 0.008). Similar associations were observed for death with a functioning graft, although not reaching statistical significance (HR = 0.47 [0.17–1.26], P = 0.13). There was a significant interaction between donor type and p2KT (P for interaction = 0.016). Indeed, p2KT was not significantly associated with the risk of graft failure from any cause including death in living donor 2KT (P = 0.39), whereas the association was substantial in the deceased donor subset (HR = 0.30 [0.14–0.64], P = 0.002). Of note, the adjusted graft survival of p2KT with deceased donor paralleled that of 2KT with living donor, either preemptive or not (93.8% vs. 88.6% at 4 years and 76.1% vs. 70.5% at 8 years, P = 0.13). This large French multicenter study analyzed using propensity scores suggests that p2KT is associated with better graft prognosis. [ABSTRACT FROM AUTHOR]

Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation is the only effective treatment. Optimal procedures have not been established for the second transplantation in this setting, however. Here we retrospectively analyzed the outcomes of 22 patients with aplastic anemia, age ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median age of patients was 36 years (range, 16 to 72 years), and the median time from the first to the second transplant was 77 days (range, 29 to 1061 days). The cumulative incidence of neutrophil engraftment at day 60 post-transplantation was 45.5% (95% confidence interval [CI], 23.6% to 65.0%). With a median follow-up of 50 months, the 4-year overall survival (OS) was 38.5% (95% CI, 18.4% to 58.5%). Mycofenolate mofetil–based graft-versus-host disease prophylaxis demonstrated greater neutrophil recovery than prophylaxis with calcineurin inhibitor alone or methotrexate-based prophylaxis (66.7% versus 37.5%; P  = .04). The use of such conditioning regimens as fludarabine + melphalan or cyclophosphamide + low-dose total body irradiation was associated with better engraftment (58.3% versus 30%; P  = .05) and better 4-year OS (55.6% versus 20%; P  = .05) than other regimens. Although further investigation is needed, umbilical cord blood could be an effective and promising option for stem cell source for urgent second transplantation in patients with aplastic anemia who develop GF after the first HSCT. [ABSTRACT FROM AUTHOR]

GF is one of the fatal complications of allogeneic HSCT. To rescue patients with primary GF, a second HSCT should be conducted as soon as possible, but the optimal donor source and technique have yet to be established. In this study, we retrospectively analyzed six children with hematologic malignancies who received TCR-haploidentical second HSCT for primary GF. The median interval between the prior HSCT and the second HSCT was 37.5 days. All patients received fludarabine and ATG containing reduced-intensity re-conditioning before the second HSCT. All patients, except one who died early, achieved both neutrophil and Plt engraftment at a median time of 15 and 33 days, respectively. Chimerism analysis showed that all engrafted patients achieved complete donor chimerism within 3 weeks. Four patients developed acute GVHD, and three patients developed chronic GVHD. TRM occurred in two patients. Median follow-up of the four survivors was 6.8 years, and all remained in sustained remission until the last follow-up. These results suggested that a TCR-haploidentical second HSCT for pediatric patients is feasible, and this approach may provide a potent option for children with primary GF. [ABSTRACT FROM AUTHOR]

A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n = 81). The indication for second HCT was graft failure after the first HCT. Transplantations were performed between 1990 and 2012. The timing of the second HCT predicted subsequent graft failure and survival. Graft failure was high when the second HCT was performed less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between the first HCT and second HCT was less than 3 months, compared with 23% when the interval was longer ( P < .001). Consequently, the 1-year survival rate was substantially lower when the interval between the first and second HCTs was less than 3 months compared with longer (23% vs 58%; P = .001). The corresponding 5-year probability of survival was 16% and 45%, respectively ( P = .006). Taken together, these data suggest that fewer than one-half of patients with FA undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to reduce the rate of graft failure after first HCT. [ABSTRACT FROM AUTHOR]

Relapse of hematological malignancies after hematopoietic stem cell transplantation (HCT) is associated with poor prognosis. A second HCT represents one of the few therapeutic options for these high-risk patients. For children undergoing second HCT, the outcome data are particularly limited. We, therefore, conducted a retrospective single-institution study and report the outcomes and prognostic variables associated with overall survival (OS) and relapse in 43 pediatric patients who underwent a second HCT between 2000 and 2013. Eleven of the 43 patients who underwent transplantation remain alive and disease-free at a median follow-up of 49 months (range, 5 to 127 months). The 5-year probability of OS for the entire cohort was 24%. Patients who had early relapse (<6 months) after first HCT had significantly worse OS than those who relapsed late (>6 months), with 5-year OS at 11% versus 34%, respectively (hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.21 to 4.93; P = .013). Active disease at time of second HCT was also associated with a significantly increased risk of relapse (subdistribution hazard ratio [SHR], 2.36; P = .049) for the entire cohort and relapse was the most frequent cause of death (23 of 32; 72%). On subgroup analysis for the 34 patients with leukemia alone, presence of active disease was associated both with a significant decrease in OS (SHR, 2.28; 95% CI, 1.02 to 5.09; P = .044) and significant increase in the rate of relapse (SHR, 2.46; P = .046). By contrast, underlying disease, donor source, conditioning regimen, or development of GVHD did not modify OS or rate of relapse. Hence, a second HCT appears to be a useful therapeutic option in children with relapsed hematological malignancies that is most likely to benefit those individuals with late onset of relapse and with low disease burden at the time of transplantation. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990 to 2010) during first or second complete remission (CR) to identify factors associated with longer postrelapse survival. Median time to post-HCT relapse was 7 months (range, 1 to 177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy alone (n = 660), donor lymphocyte infusion (DLI) ± chemotherapy (n = 202), or second alloHCT ± chemotherapy ± DLI (n = 369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 months (range, <1 to 193). Survival for all patients was 23% at 1 year after relapse; however, 3-year overall survival correlated with time from HCT to relapse (4% for relapse during the 1- to 6-month period, 12% during the 6-month to 2-year period, 26% during the 2- to 3-year period, and 38% for ≥3 years). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (relative risk, .55 for 6 months to 2 years; relative risk, .39 for 2 to 3 years; and relative risk, .28 for ≥3 years; P < .0001) and a first HCT using reduced-intensity conditioning (relative risk, .77; 95% confidence interval [CI], .66 to .88; P = .0002). In contrast, inferior survival was associated with age >40 years (relative risk, 1.42; 95% CI, 1.24 to 1.64; P < .0001), active graft-versus-host disease at relapse (relative risk, 1.25; 95% CI, 1.13 to 1.39; P < .0001), adverse cytogenetics (relative risk, 1.37; 95% CI, 1.09 to 1.71; P = .0062), mismatched unrelated donor (relative risk, 1.61; 95% CI, 1.22 to 2.13; P = .0008), and use of cord blood for first HCT (relative risk, 1.23; 95% CI, 1.06 to 1.42; P = .0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 months after their initial alloHCT had better survival and may benefit from intensive therapy, such as second alloHCT ± DLI. [ABSTRACT FROM AUTHOR]

We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplantation morbidity in this population. [ABSTRACT FROM AUTHOR]

Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). Second or subsequent allogeneic HCT using unrelated cord blood has been performed for adult patients with AML who have relapsed after a previous allogeneic HCT. Although outcomes after unrelated cord blood transplantation (CBT) as the first allogeneic HCT have significantly improved in recent years, it is unclear whether survival and engraftment improve after CBT as the second or subsequent allogeneic HCT for adult AML patients relapsing after a previous allogeneic HCT. The objective of this retrospective study was to evaluate trends of survival and other transplantation outcomes after single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT over the past 19 years in Japan. We retrospectively assessed survival trends and other outcomes of single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT according to the time period of CBT (2001-2007, 2008-2013, or 2014-2019) using a nationwide Japanese database. The median age was 45 years among 1109 CBTs, and 844 (78.6%) patients were not in complete remission at the time of CBT. Over the 3 time periods, there was a progressive increase in higher cryopreserved cord blood total nucleated cell dose and myeloablative conditioning regimens. The 2-year overall survival was 14.0% in 2001-2007, 19.9% in 2008-2013, and 24.4% in 2014-2019 (P <.001 by log-rank trend test). The 2-year relapse-related mortality was 54.0% in 2001-2007, 44.4% in 2008-2013, and 39.1% in 2014-2019 (P < 0.001 by Gray's test), but nonrelapse mortality was not significantly different across the time periods (P = 0.557 by Gray's test). The 42-day neutrophil engraftment also significantly improved (62.9% in 2001-2007, 69.7% in 2008-2013, and 79.9% in 2014-2019; P < 0.001 by Gray's test). Our data demonstrate significant improvements in overall and relapse-related mortality, as well as neutrophil engraftment, after single-unit unrelated CBT as a second or subsequent allogeneic HCT for adult patients with AML relapsed after previous allogeneic HCT over the past 19 years., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Graft failure (GF) remains a major problem in cord blood transplantation (CBT). In 36 adult patients undergoing CBT at our hospital between July 2003 and December 2009, six patients developed GF (primary, n = 5; secondary, n = 1). All six patients underwent second stem cell transplantation (SCT). Three patients had acute myeloid leukemia, one had acute lymphoblastic leukemia, one had chronic myeloid leukemia, and one had aplastic anemia. Five patients were complicated with sepsis before the second SCT. The median elapsed time from first CBT to the diagnosis of primary GF was 27 days. Secondary GF was diagnosed on day 567. The median elapsed time from primary GF to second SCT was 9 days. In the patient with secondary GF, the elapsed time was 35 days. Cord blood grafts were used in 5 patients and a matched sibling donor in one patient. All 6 patients underwent second transplantation following a modified '1-day'-based preparative regimen consisting of fludarabine (30 mg/m(2), 1 day, n = 2; 2 days, n = 1; 3 days, n = 3), cyclophosphamide (2 g/m(2)), and total body irradiation (2 Gy). All patients achieved neutrophil engraftment, and the median elapsed time from second SCT to engraftment was 35 days. Four patients remain alive between 5 and 38 months after second SCT. '1-day'-based short-term conditioning may be a promising salvage regimen. [ABSTRACT FROM AUTHOR]

Human herpes virus (HHV)6-associated limbic encephalitis and/or myelitis is one of the life-threatening central nervous system complications following allogeneic hematopoietic stem cell transplantation (HSCT). Recent reports have shown significant correlations of these complications with unrelated cord blood transplantation (UCBT). We retrospectively analyzed 228 allogeneic HSCT recipients in our single institution; 13 patients (5.7%) were diagnosed with HHV6-associated encephalitis/myelitis. This complication was documented in 8 of 51 UCBT recipients (15.7%) and 5 of 177 recipients (2.8%) transplanted with bone marrow or peripheral blood stem cells, indicating a higher incidence of this complication occurring in UCBT recipients (P = .0005). In addition, HHV6-associated encephalitis/myelitis occurred more frequently in recipients who underwent 2 or more HSCTs (7 of 59 recipients [11.9%]), compared to those who received only 1 HSCT (6 of 169 recipients [3.6%], P = .018). Of note, the incidence of this complication increased to 28.6% (6 of 21 recipients), when the analysis was restricted to a second or more UCBT recipients. All 13 patients presented preengraftment immune response prior to the onset of encephalitis. Two patients manifested typical symptoms at the onset of HHV6-associated encephalitis/myelitis, such as memory dysfunction, disorientation, and consciousness disturbance. However, 4 patients presented only with dysesthesia and pruritus, described as typical manifestations of patients with calcineurin-inhibitor-induced pain syndrome (CIPS), and the remaining 7 showed both symptoms, indicating that CIPS-like symptoms might be manifestations of HHV6-associated myelitis. Thus, physicians should be alert to this rare but often fatal complication, particularly for those who receive 2 or more HSCTs using UCB. [ABSTRACT FROM AUTHOR]

Abstract: We examined transplantation outcomes after a second HLA-matched sibling transplantation for primary (16%) or secondary (84%) graft failure in 166 patients with severe acquired aplastic anemia (AA). Two-thirds of these patients has a performance score < 90. In most cases (88%), the same donor was used for both transplants, for both transplantations, and 84% of the second transplantations used bone marrow grafts. We identified 2 prognostic factors: intertransplantation interval (surrogate for primary graft failure and early secondary graft failure) and performance status. Shorter intertransplantation interval (≤ 3 months) and poor performance score (< 90) at second transplantation were associated with high mortality. In patients with a performance score of 90% to 100%, the 8-year probability of overall survival (OS) after second transplantation ≤ 3 and > 3 months from first transplantation was 56% and 76%, respectively. The corresponding probabilities in patients with lower performance scores were 33% and 61%. The predominant cause of failure after second transplantation was nonengraftment (in 72 of 166 patients), most commonly in patients with primary or early secondary graft failure (51 of 72; 71%). Our data indicate that novel approaches, including conditioning regimens with greater immunosuppression, should be explored for these patients. [Copyright &y& Elsevier]

The Japan Cord Blood Bank Network (JCBBN) reports the treatment of 22 children with acute myeloid leukemia (AML) who received umbilical cord blood transplantation from unrelated donors (CBT) as their second hematopoietic stem cell transplantation (HSCT). Provided by the JCBBN, between February 1997 and September 2006, 22 patients had CBT as a second HSCT. In the initial HSCT, eight received autologous, seven received CBT, and the remaining had allogenic BMT. At the time of CBT as a second HSCT, seven were in the second complete remission (CR2), two in the third CR (CR3), the remaining were not in remission. Reduced intensity conditioning (RIC) conducted for 10 cases and myeloablative conditioning (MAC) for 12 cases. The overall survival rate was 31.3%, 5 years after CBT. Second complete remission at second transplantation was favorable prognosis (58.3 +/- 18.6%, compared with 17.1 +/- 10.8% for the non-CR group. Mortality after CBT as a second HSCT accounted for 15 cases, 8 from treatment-related mortality. In conclusion, CBT combined with RIC as second HSCT may be useful against a recurrence of AML in children after the initial HSCT. [ABSTRACT FROM AUTHOR]

Donor-specific anti-HLA antibody and anti-blood group antibody could cause antibody-mediated rejection (AMR). Here, we report a successful second ABO-incompatible (ABO-I) renal transplantation in a patient with donor-specific anti-HLA antibody and its pathologic findings. A 50-yr-old woman underwent second ABO-I (A1 to O) renal transplantation. She had received the first renal graft from her mother following splenectomy in July 2003; however, graft function was lost 50 d after transplantation because of AMR. The patient received the second renal graft in November 2005, from her husband whose blood type was also A1. The recipient had donor-specific anti-HLA antibody because flow panel reactive antibody and flow cytometry crossmatch were strongly positive prior to the plasmapheresis (PP) therapy. Pre-transplant intensive immunosuppression, PP, and low dose (100 mg/m2) anti-CD20 antibody (rituximab) administration were performed as desensitization therapy. The recipient clinically developed acute rejection, and allograft biopsy specimen at day 6 post-transplant revealed AMR type II according to the Banff 2003 classification. However, the graft function was rescued by PP/low dose (100 mg/kg) intravenous immunoglobulin (IVIG) therapy, and the biopsy specimen at day 43 post-transplant showed border-line change without AMR. Rituximab and PP/low-dose IVIG therapy might improve the clinical course and pathologic findings in this AMR-related high-risk transplantation. [ABSTRACT FROM AUTHOR]

We reviewed the medical records of 123 adult reduced-intensity cord blood transplantation (RI-CBT) recipients to investigate the clinical features of graft failure after RI-CBT. Nine (7·3%) had graft failure, and were classified as graft rejection rather than primary graft failure; they showed peripheral cytopenia with complete loss of donor-type haematopoiesis, implying destruction of donor cells by immunological mechanisms rather than poor graft function. Three of them died of bacterial or fungal infection during neutropenia. Two recovered autologous haematopoiesis. The remaining four patients underwent a second RI-CBT and developed severe regimen-related toxicities. One died of pneumonia on day 8, and the other three achieved engraftment. Two of them died of transplant-related mortality, and the other survived without disease progression for 9·0 months after the second RI-CBT. In total, seven of the nine patients with graft failure died. The median survival of those with graft failure was 3·8 months (range, 0·9–15·4). Graft failure is a serious complication of RI-CBT. As host T cells cannot completely be eliminated by reduced-intensity preparative regimens, we need to be aware of the difficulty in differentiating graft rejection from other causes of graft failure following RI-CBT. Further studies are warranted to establish optimal diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

We present the case of a patient with myelodysplastic syndrome who experienced leukemia transformation and subsequently underwent transplantation of unmanipulated peripheral blood stem cells from a haploidentical sibling mismatched at 3 HLA antigens, along with a reduced-intensity regimen (fludarabine, busulfan, and anti-T-lymphocyte globulin) and tacrolimus-containing graft-versus-host disease (GVHD) prophylaxis. The patient experienced graft rejection but successfully underwent a second transplantation from the same donor with a slightly intensified conditioning regimen. Although the patient developed life-threatening cytomegalovirus (CMV) pneumonia following the second transplantation, he recovered completely from the pneumonia with intensive supportive therapy. He is still in complete remission past day 1000 in the absence of GVHD. As far as we know, this report is the first to describe a successful second transplantation that was performed for graft rejection following HLA-haploidentical nonmyeloablative stem cell transplantation. Furthermore, we emphasize that patients should be carefully monitored for CMV infection when reduced-intensity conditioning is given repeatedly over a short period. [ABSTRACT FROM AUTHOR]

Summary:Treatment options for persons with leukemia relapsing after allogeneic transplantation are limited. We analyzed the outcome of 279 patients with acute and chronic leukemia, who relapsed after HLA-identical sibling transplantation and received a second allogeneic transplant. The influence of potential risk factors on treatment-related mortality (TRM), relapse, treatment failure (relapse or death) and overall survival after second transplantation were assessed using proportional-hazards regression. The cumulative incidences (95%confidence interval) of relapse and TRM at 5 years were 42 (36-48)%and 30 (24-36)%, respectively. The 5-year probabilities of both overall and leukemia-free survival were 28 (23-34)%. In multivariate analyses, risks of treatment failure and mortality were lower in younger patients (?20 years) and patients who relapsed after 6 months from first transplantation. Risks of relapse were lower in patients who relapsed after 6 months from first transplantation and in complete remission prior to second transplantation. Risks of relapse were higher after reduced-intensity conditioning regimens. Any potential advantage of using a different matched related donor for a second transplantation is not supported by these data. Although age, disease status and conditioning regimen are important, duration of remission after first transplantation appear to be the most important determinant of outcome.Bone Marrow Transplantation (2004) 34, 721-727. doi:10.1038/sj.bmt.1704645 Published online 23 August 2004 [ABSTRACT FROM AUTHOR]

Recurrent acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HSCT) predicts a dismal prognosis. We sought to determine whether a second HSCT would result in long-term disease-free survival with acceptable toxicity. We evaluated the outcome of a second HSCT with a preparative regimen of cyclophosphamide and total body irradiation in pediatric patients with AML who relapsed after an initial HSCT with a busulfan and cyclophosphamide preparative regimen. Twenty-five patients aged 1.1 to 17.2 years (median, 4.1 years) with AML received a second HSCT for recurrent disease. All patients were conditioned with busulfan and cyclophosphamide for the first HSCT and with cyclophosphamide and total body irradiation for the second HSCT. Donor sources for the first HSCT were autologous (n = 11) or allogeneic (n = 14), whereas all donors for the second HSCT were allogeneic (12 matched related, 9 mismatched related, and 4 unrelated). Engraftment after the second HSCT occurred in all patients at median of 19.0 days (range, 11–32 days). The cumulative incidence of grade II to IV graft-versus-host disease was 76% after the second HSCT. Three patients died from regimen-related toxicity before day 100, 9 relapsed at a median of 5.4 months (range, 1.8–34.0 months), and 12 survived a median of 9.1 years (range, 7.0–14.4 years) after the second HSCT. The Kaplan-Meier estimates of survival at 100 days, 1 year, and 10 years were 88%, 56%, and 48%, respectively. The disease-free survival rate at 10 years was 44%. Multivariate Cox regression analysis suggested that patients who received a second HSCT in relapse had a relative risk of relapse of 7.8 (P = .02) compared with patients who underwent transplantation in remission. In addition, patients who received their second HSCT ≤6 months after the first transplantation were at increased risk of relapse (P = .03). These data suggest that second HSCT after a failed initial transplantation results in long-term disease-free survival in one half of children with relapsed AML. Because a higher tumor burden at the time of second HSCT was associated with a higher risk of subsequent relapse, patients might benefit from reinduction therapy before the second HSCT. [Copyright &y& Elsevier]

We describe the case of a 51-year-old patient with relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation (BMT), who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) after conditioning with a novel regimen consisting of fludarabine, busulfan, and antithymocyte globulin. The second PBSCT was performed early, at 3 months after the initial allogeneic BMT, but it was well tolerated and complete hematologic remission was documented. The patient did not experience any early transplantation-related organ toxicity but died from opportunistic infection 6 months after the second transplantation. Our experience suggests that this novel regimen may induce remission and could be offered to patients relapsing after the first transplantation; however, the fludarabine-containing regimen might be accompanied by profound immunosuppression. [ABSTRACT FROM AUTHOR]

Choeyprasert W, Pakakasama S, Anurathapan U, Songdej D, Sirachainun N, Sirireung S, Panthangkool W, Hongeng S. The second mini-transplant for unstable mixed chimerism within the first 100 days after hematopoietic stem cell transplant in severe thalassemia. Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract: Allogeneic HSCT is the only curative treatment for severe thalassemia disease. MC occurs in one-third of these patients within the first two months after HSCT; this is a major risk factor of graft rejection, especially when RHCs are more than 25%. There is still no consensus for the management of MC, especially in the early phase of HSCT. The DLI has also been described in the treatment of MC following HSCT for hemoglobinopathies, but its success is still not guaranteed. The second HSCT has been an approach used in an attempt to cure patients who reject their graft. Concern about toxicity of conditioning regimen, the second HSCT is usually delayed for at least a year after the first HSCT. We would like to demonstrate the successful use of the second mini-allogeneic HSCT in hemoglobin E/β-thalassemia with evidence of unstable MC in the first 100 days after allogeneic HSCT to prevent further graft loss after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

Abstract: There are many reports of second allogeneic stem cell transplantation (allo-SCT) using cord blood (CB) for graft failure after initial allo-SCT. However, the efficacy of second allo-SCT using CB for patients with leukemia relapsed after initial allo-SCT is unknown. We report the results of second allo-SCT using CB in seven adult patients with leukemia relapsed after initial allo-SCT. All patients received a myeloablative conditioning regimen including oral busulfan 16mg/kg, intravenously fludarabine 100mg/m2 and cyclophosphamide 120mg/kg. All but one patient had myeloid reconstitution and four patients remain alive at between 4 and 40 months after second SCT. We conclude that second myeloablative allo-SCT using CB may be feasible in selected patients with the relatively younger age, less organ damage and longer time interval between first and second allo-SCT. [Copyright &y& Elsevier]

A 38-yr-old man with chronic renal failure received a second kidney transplantation from a cadaveric donor. Complement-dependent cytotoxicity cross-match (CDC) was negative against T cells, but positive with the B-cell warm test. Human leukocyte antigen (HLA)-typing showed a one haplo-identical match. The blood type was compatible. He was treated with tacrolimus, mycophenolate mofetil (MMF), methylpredonisolone (MP), and basiliximab as immunosuppressive therapy. A clinical episode graft biopsy and Flow-PRA on post-operative day (POD) 19 showed anti-HLA antibody-mediated acute rejection (AHR). The patient was treated with plasmapheresis (PP). Renal biopsy performed on POD 65 because of re-rise of serum creatinine level showed worsening of renal injury. The patient was treated with rituximab (100 mg/body) with PP and MP pulse therapy, followed by tacrolimus and MMF. Graft function thereafter improved. A renal allograft biopsy specimen on POD 300 and Flow-PRA showed the remission of AHR within one-yr after transplantation. [ABSTRACT FROM AUTHOR]

A 7-year-old girl with acute myelogenous leukemia with multilineage dysplasia received unrelated cord blood transplantation but developed hemophagocytic syndrome (HPS) after sepsis with methicillin-resistant coagulase-negative staphylococci before engraftment. Bone marrow aspiration on day 20 revealed a markedly increased number of activated macrophages showing hemophagocytosis. The presence of donor-type chimera in the bone marrow was confirmed at that time. We therefore quickly started immunosuppressive and antibacterial treatment. Although her condition gradually improved, the patient suffered graft failure due to HPS. She received peripheral blood stem cell transplantation from her HLA 2-loci-mismatched mother on day 54 and continued in complete remission 12 months after the second transplantation. The results in this case suggested that because of fetomaternal microchimerism it may be useful to select an HLA-haploidentical mother as a backup donor for stem cell transplantation. [ABSTRACT FROM AUTHOR]

Graft failure (GF) is a fatal complication of allogeneic stem cell transplantation, especially after haploidentical transplantation. The mortality of GF is nearly 100% without an effective salvage method. A second transplantation is usually necessary to save the patient's life. However, there is no standardized regimen, and the outcome is usually disappointing. We report on a prospective single-center study using a reduced-intensity conditioning regimen with different haploidentical donors (HIDs). Patients with GF after the first transplantation were enrolled in a prospective single-arm clinical trial (ClinicalTrials.Gov ID: NCT03717545) at the Peking University Institute of Hematology. The conditioning regimen consisted of fludarabine (30 mg/m 2 ) (days-6 to-2) and cyclophosphamide (1,000 mg/m 2 /day) (days-5 to-4). Patients underwent a second transplant from a different HID using a granulocyte colony-stimulating factor primed bone marrow and peripheral blood stem cells. The primary outcome was neutrophil engraftment at day 28. The secondary outcomes included platelet engraftment at day 100, transplant-related mortality (TRM) at day 30, TRM at day 100, and overall survival (OS) at 1 year. From March 2018 to June 2020, 13 patients were enrolled in this clinical trial. Of the 13 patients, five had acute myeloid leukemia, five had acute lymphoblastic leukemia, two had myelodysplastic syndromes, and one had a non-Hodgkin lymphoma. The median age at first transplantation was 38 years (range, 8-55 years). As for the first transplantation, 11 patients underwent haploidentical transplantations and two underwent unrelated donor transplantations. At the time of GF, three patients had complete donor chimerism, five had mixed chimerism, and five had complete recipient chimerism. The median time from the first transplantation to the second transplantation was 49 (range 35-120) days. The medians of infused cell doses were as follows: mononuclear cells 7.93 (5.95-12.51) × 10 8 /kg and CD34 + cells 2.28 (0.75-5.57) × 10 6 /kg. All 13 patients achieved neutrophil engraftment after the second transplantation, with a median engraftment time of 11 (range 10-20) days after transplantation. The platelet engraftment rate on day 100 after transplantation was 76.9%. The TRMs at day 30, day 100, and 1-year were 0, 0, and 23.1%, respectively. The OS and disease-free survival at 1-year were 56.6 and 48.4%, respectively. For patients with GF after first transplantation, a second transplantation using a fludarabine/cyclophosphamide regimen from a different HID was a promising salvage option. Further investigation is needed to confirm the suitability of this method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sun, Wang, Wang, Yan, Cheng, Chen, Zhang, Han, Han, Suo, Xu, Zhang, Liu and Huang.)

Background: Donor mixed chimerism (MC) is an increasing problem after hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases., Procedure: In this study, a self-administered questionnaire was used to retrospectively compare efficacy and safety in 49 patients undergoing second HSCT (n = 13) or donor lymphocyte infusion (DLI; n = 36) as treatment for MC., Results: The response rate to DLI of patients with secondary graft failure (GF) (25.0%) was significantly lower than that of patients without secondary GF (81.3%; P = 0.041). Among patients undergoing DLI, the rates of successful response were significantly higher in patients having at least 30% donor chimerism (94.1%) than in patients having less than 30% donor chimerism (61.1%; P = 0.041). Furthermore, the rates of successful response were significantly higher in patients receiving larger first or maximum doses of DLI. Sixteen (50.0%) of 32 patients without secondary GF attained complete chimerism after DLI. The cumulative incidence of grade II-IV acute graft-versus-host disease and cytopenia was 37.6 and 26.1%, respectively., Conclusions: DLI yields promising response rates in most patients with higher donor chimerism levels, whereas second HSCT is more likely to benefit patients with lower donor chimerism levels., (© 2016 Wiley Periodicals, Inc.)