The 8th National Hematology Conference, facing the lymphoma hematopoietic stem cell transplant application dilemma, how can blood doctors break the situation?

The 8th National Blood Tumor Congress was successfully concluded from October 16th to October 18th, 2020, and the experts gathered hundreds of flowers to bring us an academic feast.
Professor Zhai Dehui from the Hematology Hospital of the Chinese Academy of Medical Sciences brought us the topic of "Dilemma and Breakthrough in the Application of Hematopoietic Stem Cell Transplantation in China", which is comprehensively organized from the content of this lecture in order to reach the readers.
, China still needs to work hard according to the international bone marrow transplantation registry data, the main method of hematopoietic stem cell transplantation in the United States is auto-stem cell transplantation (Auto-SCT), 2018 registration data show that Auto-SCT is 14006 cases, allo-SCT 9028 cases; the European Society for Blood and Bone marrow Transplantation (EBMT) annual report 2019 is similar to that of the United States, where there has been a significant increase in somatic stem cell transplants (ASCT) in the last 20 years, with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) accounting for more than 80%.
, china is different from Europe and the United States, mainly Allo-SCT, the same period registration data show auto-SCT for 2723 cases, Allo-SCT for 9597 cases.
the number of cases, the number and ratio of lymphoma ASCT in China is still far lower than in Europe and the United States, there is still a lot of room for development.
, the five-year survival rate of lymphoma patients in China is about 30%, while in Europe and the United States it is as high as 60-70%.
In China, data from Beijing Cancer Hospital show a five-year survival rate of 62%, close to the level of developed countries in Europe and the United States, mainly due to two aspects: first, the establishment and continuous improvement of the norms, including hematopoietic stem cell transplantation, overall treatment strategy, and second, a number of new drug clinical trials.
Figure 1: Guidelines recommend the selection of hematopoietic stem cells for different types of tumors The results of recent research of the Hematology Hospital of the Chinese Academy of Medical Sciences are at a glance★ ≤ The international prognosis index (IPI) of lymphoma or the age-adjusted international prognostic index (aaIPI) score was high-risk or high-risk group, double expression lymphoma (DEL)/double-percussive lymphoma (DHL), ki-67≥80%, and medium-term (after 3-4 course of treatment) PET-CT evaluation was not fully alleviated (CR).
participants was 40 (14-63) years old.
results showed that the CR rate before transplantation was 84.1% (53/63), 57 patients (90.5%) after transplantation obtained CR, and the average two-year progress-free survival (PFS) was found after 50 months of follow-up, with a two-year total survival (OS) rate of 92.1%, and five-year PFS and OS at 92.8% and 83.5%, respectively.
aaaIPI is a bad prognostic factor for OS, and bone marrow aggression (bone marrow pathology detects lymphocyte aggression) is a bad prognostic factor for PFS and OS.
★ MCL young patient researchers treated 30 patients through the group (Figure 2), of whom 56.7% (17/30) had ASCT, an induced response rate of 100%, and a high rate of 86% of CR-CRu.
follow-up as of August 2020, with a medium follow-up of 45.5 months.
three-year PFS and OS were 74% and 96%, respectively.
Figure 2: Young MCL Research Program of Hematology Hospital of Chinese Academy of Medical Sciences★ Clinical analysis of autologous stem cell transplantation of extrinsic T-cell lymphoma included 16 cases of non-special finger type (PTCL-U) of extrinsic T-cell lymphoma, 4 cases of hemangioblast lymphoma (AITL), 3 cases of ALK-negative mesoplasmic cell lymphoma (ALCL) and 2 cases of hepatic T-cell lymphoma.
2 patients with hepatic spleen T-cell lymphoma were all phase IV B cases, and CR1 parallel ASCT consolidation therapy was obtained after combined chemotherapy, but all relapsed and died early within 12 months after transplantation.
the rest of the patients CR1 ASCT group (17 cases), 3 years OS 80.2% ±10.4%, CR2 ASCT group (6 cases) 3 years OS 50.0% ±2 0.4%; 3-year OS was 84.4% ±10.2% in the bone marrow-free aggression group and 53.3% ±17.3% ±17.3% in the 3-year OS.
the efficacy of ASCT and chemotherapy in CR1 patients was further compared recently, with four-year PFS for ASCT treatment and chemotherapy patients at 59.8 and 32.4%, respectively, and four-year OS at 67.7% and 44.4%, respectively.
★ Clinical analysis of self-hematopoietic stem cell transplantation in patients with lymphocyte lymphoma in 30 patients with high-risk lymphocyte lymphoma, the induction stage of the overall treatment of acute lymphoblastic leukemia after treatment to obtain CR, follow-up ASCT intensive consolidation therapy can significantly improve survival rate, 5 years PFS and OS are as high as 77.8%.
★ 2016, the hematology hospital of the Chinese Academy of Medical Sciences observed the effect of GBC/GBM alternative pretreation scheme on patients with lymphoma, the safety analogy of the classic BEAM/BEAC scheme, and the first-line ASCT MCL, The two-year PFS of DLBCL and PTCL were close to or above 90%, while Hodgkin's lymphoma (HL) was the most effective in second-tier ASCT (2-year PFS 82%) and DLBCL was more satisfactory (2-year PFS 67%).
can we improve the efficacy of ASCT transplantation? ★ The Chinese Expert Consensus on hematopoietic stem cell transplantation for the treatment of lymphoma (2018 edition) mentions that DLBCL hematopoietic stem cell transplantation is an adaptation certificate: Young high-risk DLBCL, ASCT can be used as a first-line consolidation treatment strategy; To save DLBCL for treatment-sensitive primary or primary relapse/difficult treatment (partial remission of first-line induced treatment response (PR), stabilization (SD), or disease progression (PD), ASCT should be a solid treatment strategy appropriate to patient standards.
★ recommends ASCT for second-line treatment for DBCL: NCCN guidelines.
factors that affect the survival of transplant patients? ★ Early recurrence/difficult-to-treat lymphoma-related studies have shown that early relapse/difficult-to-treat patients, i.e. those with high aaIPI scores, first-line R therapy and rescue therapy, did not receive CR/CRu (Figure 3), the survival rate of those with late recurrence decreased significantly, and the survival rate of patients with Ritriximab therapy improved.
Figure 3: Factors Affecting Survival (CORAL) ★ Pre-transplant PET/CT Remission Status There were studies in which 105 cases of DBCL/TFL were selected, 49 cases of pre-transplant PET positive (47%), 56 cases of negative (53%), of which PET-positive vs. PET negative, 4 years PFS is 32% and 64% (P - 0.0002), 4 years OS is 56% and 75% (P - 0.025), so patients should get CR as soon as possible ASCT.
other biological markers: PFS and OS decreased significantly in patients with MYC plus, R/R DEL, and DHL (Figure 4).
Figure 4: Other biological markers★ summarize the possible factors that affect the efficacy of salvage ASCT: previous chemotherapy has not obtained CR, especially in patients with primary drug resistance;
new drug era of traditional rescue treatments and new drugs provides more means for patients to have access to CR after ASCT.
2018, the number of DBCL patients receiving second-line rescue ASCT treatment in the United States decreased by 45% compared to previous years, possibly due to the choice of CAR-T treatment for patients who did not reach CR after second-line rescue treatment (Figure 5).
5: Trends in the application of ASCT in DBCL in the United States, what is the study of the effectiveness of ASCT treatment in patients with chemotherapy-sensitive recurrence of PET/CT-PR before transplantation? Findings from the International Bone Marrow Transplant Registry at the 2020 ASCO Annual Meeting.
adjusted five-year PFS and OS did not differ significantly in the early chemotherapy failure group (ECF) and the late chemotherapy failure group (LCF), and the cumulative recurrence rate over five years was similar in both groups (Figure 6).
PFS rate for the five-year period was 41 per cent, while the five-year OS rate was 51 per cent to 63 per cent.
suggests that saving treatment-sensitive patients, even if the rescue treatment fails to meet CR, the salvage ASCT consolidation treatment is still the current standard consolidation treatment strategy.
6: 5 years PFS and OS in the ECF group and LCF group are not significantly different for this group of patients, the National Comprehensive Cancer Network (NCCN) guidelines recommend alternative CAR-T treatment.
ZUMA-7 study is also exploring how to choose a rescue treatment for such patients because of the high cost and safety of CAR-T treatments that need to be improved (Figure 7).
group criteria for patients who have previously received treatment that includes cyclocymoids and lysoxi monoantigens, excluding patients who are not resistant to first-line chemotherapy.
Figure 7: ZUMA-7: CAR-T vs Definition of Saving Chemotherapy Joint Transplant Tip Difficulty: a. The best outcome after first-line treatment is PD; b. The best efficacy after at least 2 cycles of first-line chemotherapy is SD; c. The best efficacy after at least 6 cycles of chemotherapy is PR and biopsy confirms tumor residue, or PD within 1 year;
For patients with early recurrence difficulty or multi-line DLBCL relapse, we are trying CAR-T (CNCT19) combined with ASCT, which has a significantly higher CR rate (71.4%) for patients receiving ASCT Sequenty CNCT19 infusions than for individual CNCT19 therapy (about 40% CR rate) over the same period.
and its security is controlled.
maintenance treatment for post-ASCT DLBCL patients: DLBCL patients are not recommended for Rituximab as a first-line treatment, whether they are relapsed/difficult to treat or high-risk patients with initial treatment.
in the choice of first-line treatment, the NCCN guidelines remove ASCT, possibly because the results of four randomized controlled studies over the past decade have been negative (Table 1), but doesn't that mean it has lost value? Especially in China, the focus is on the research of R-CHOP and new drug X, but in fact is still in a predicament, there are no clear results, review the past research, subgroup analysis such as really high-risk patients, MYC IHC plus and DPL patients first-line ASCT can still significantly improve the efficacy of patients.
Table 1: First-line immunothermoury compared to HDT/ASCT for Patients with Lymphoma in China, ASCT is very safe and cost-controllable, China's new drug accessability is much lower than in developed countries such as Europe and the United States, and until the relapse difficult stage patients have no economic conditions to accept ASCT, so for China's young high-risk DLBCL patients first-line ASCT treatment has its value and status.
for FL (filter lymphoma), early recurrence FL survival outcomes are poor, so the benefits of early ASCT survival are more significant.
for PTCLs patients, a retrospective analysis of 82 patients found that ASCT during chemotherapy sensitivity and remission was closely associated with 3 years of OS, with chemotherapy being 58 percent sensitive: chemotherapy insensitive at 36 percent.
, several studies in recent years have shown that ASCT achieves better long-term survival after cr.
How is hematopoietic stem cell therapy used in HL? . . ASCT is a suitable adaptation for patients who fail to achieve CR or save treatment sensitivity; patients with early recurrence after first-line treatment (<12 months) have poor prognosis; and good prognosis for patients with PET/CT negativeness before transplantation; ASCT post-consolidation therapy (e.g. BV) is one of the ways to improve efficacy, especially in high-risk patients with early recurrence/progression; RIC-allogenic SCT is recommended for patients who relapse after ASCT.
because the price is more popular, the exploration of PD-1 monoantigen treatment before and after ASCT is more common in China.
Finally, Professor Gong concluded: Similar to multiple myeloma, we have entered the new drug era, but traditional treatment can not be completely replaced by new drugs, better combination of these means can achieve better results, even in the new drug era, ASCT also plays an important role in the overall treatment of the disease.
the benefits of ASCT for different diseases, especially the NHL is a highly heterogeneic disease that needs to be further analyzed by subsype and treatment timing.
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