[Impact of disease status on outcomes of allogeneic hematopoietic stem cell transplantation in patients with refractory and relapsed acute myeloid leukemia].

The study was aimed to evaluate the impact of disease status on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory and relapsed acute myeloid leukemia (AML). 32 patients with refractory and relapsed AML received allo-HSCT after myeloablative conditioning regimen, including 17 patients in no-remission (NR) and 15 patients in complete remission (CR) at the time of transplant. Treatment related adverse events, relapse rate and leukemia free survival (LFS) were analyzed. The results showed that the parameters of sex, age, cytogenetic risk and transplant procedures were comparable between the two groups. 30 patients had successful engraftment, except one had graft failure and one died from severe veno-occlusive disease in the NR group. The incidences of aGVHD in NR group and CR group were 47.1% (8 patients) and 33.5% (5 patients) respectively. Out of comparable patients, 5 from 9 patients in NR group developed with cGVHD, and 4 from 11 patients in CR group were subjected to cGVHD. There were no statistic difference in incidences of aGVHD and cGVHD between two group. Compa-red with CR group, NR group had a higher treatment-related mortality (29.4% vs 14.3%, P = 0.392) and relapse rate (42.9% vs 26.7% P = 0.300), but there was no significant difference. With a median follow-up of 13 (1 - 124) months, 6 patients remained alive in both of the two groups, and the 2 year LFS of them were parallel (35.3% vs 40.0%, P = 0.267). Among these 32 patients, overall survival (OS) was better in patients with age < 35 years (P = 0.044) and with the appearance of cGVHD (P = 0.046). It is concluded that allo-HSCT is an effective salvage therapy for patients with refractory and relapsed AML, and the overall outcome seems unrelated to the disease status (NR or CR) before transplantation. As such, for refractory and relapsed AML patients in non-remission, performance of allo-HSCT to achieve long-term survival is feasible.

[Correlation between clinical outcome and WT1 detection after hematopoietic stem cell transplantation in acute leukemia].

OBJECTIVE: To evaluate preliminarily the significance of detecting the Wilms' tumor (WT1) gene level on monitoring minimal residual disease (MRD) and predicting the clinical outcome in patients of acute leukemia following hematopoietic stem cell transplantation (HSCT). METHODS: The mRNA expression levels of WT1 and house-keeping gene ABL were dynamically measured with Real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) on 326 bone marrow samples from 63 post-HSCT patients in our hospital from December 2001 to September 2009. After comparing the WT1 levels of patients with different post-transplantation outcomes, the investigators used the receiver operating characteristic (ROC) curve to determine the WT1 threshold so as to predict their clinical relapses. Then different prognoses of WT1 positive and negative patients were analyzed. RESULTS: The levels of WT1 expression showed significant difference between the 19 relapsing and 44 non-relapsing patients with the median expression levels of 1270 (55 - 47 596) and 132 (0 - 2959) respectively (P < 0.01). In 19 relapsing patients, except for 1 patient discontinuing the detection of WT1, 10 mortality cases due to recurrence had higher levels of WT1 expression than other 8 patients (P > 0.05). According to the ROC curve, the cut-off value of WT1 at 585 could separate 63 patients into the WT1-positive group (> 585) and the WT1-negative group (≤ 585). The WT1-negative group was found to have a longer relapse-free survival (RFS) and overall survival (OS) than the positive group (all P < 0.01). Twenty-one WT1-positive patients were followed up for 3, 4 - 6, 7 - 9 and 9 months respectively. The cumulative post-HSCT recurrence rates in those WT1-positive cases were 8/8, 2/4, 2/4 and 3/5 (P = 0.063) respectively. And the intervention was ineffective. CONCLUSION: WTl gene may be an independent factor of monitoring MRD. And WT1 > 585 is a poor post-HSCT prognostic factor for the patients of acute leukemia.

[Detecting minimal residual disease status in allogeneic hematopoietic stem cell transplantation of patients with high-risk acute leukemia].

OBJECTIVE: To explore the relationship between minimal residual disease (MRD) and the outcome of patients with high-risk acute leukemia (AL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: By 4/5-color multi-parameter flow cytometry (MFC, CD45/SSC gating) for detecting MRD at pre-(day-30) and post-transplant (day +30, +60, +100, 6 months, 9 months and 12 months), the investigators retrospectively analyzed the MRD levels and the prognosis of 90 high-risk patients. According to the MRD cutoff value of 0.1%, the low-level and high-level groups were defined. In the high-level group, the patients were divided into two sub groups according to the subsequent treatment (intervention therapy group and non-intervention therapy group). RESULTS: MRD pre-transplant had no predictive value for the clinical outcome. The patients with high levels of MRD post-transplant (+60 d and +100 d) showed higher relapse rates than those of the low-level group. In addition, regarding MRD +100 d post-transplant, differences were significant among 3 groups (high-level MRD and intervention therapy group, high-level MRD and non-intervention therapy group and low-level MRD group) including 1-year relapse-free survival (RFS) (100% vs 60.87% vs 91.30%, P < 0.05) and 3-year RFS (85.71% vs 44.72% vs 68.48%, P < 0.05). The median time from first high level MRD detected to clinical relapse was 2.5 (1 - 26) months. In the high level MRD group (+100 d post-transplant), 7 of 30 patients received intervention therapy without relapse. However another 23 patients had no intervention treatment and 11 of them relapsed latter (P < 0.05). CONCLUSION: The MFC-based quantification of MRD post-transplant reveals important prognostic information in patients with high-risk AL. MRD check point at day +100 (cutoff: 0.1%) may discriminate different risk populations. Those patients with MRD levels ≥ 0.1% should receive early intervention at an early stage and a low tumor burden so as to reduce the relapse rate and boost survival.