scholarly journals Risk Stratification, Measurable Residual Disease, and Outcomes of AML Patients with a Trisomy 8 Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5679
Author(s):  
Donata Backhaus ◽  
Madlen Jentzsch ◽  
Lara Bischof ◽  
Dominic Brauer ◽  
Christina Wilhelm ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Consolidation Therapy ◽  
Trisomy 8 ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Measurable Residual Disease

Background: For most patients with acute myeloid leukemia (AML) harboring a trisomy 8 an allogeneic hematopoietic stem cell transplantation (HSCT) is a suitable and recommended consolidation therapy. However, comparative outcome analyses between patients with and without trisomy 8 undergoing allogeneic HSCT have not been performed so far. Methods: We retrospectively analyzed clinical features, outcomes, and measurable residual disease (MRD) of 659 AML (12%, n = 81, with a trisomy 8) patients subjected to allogeneic HSCT as a consolidation therapy. Results: The presence of a trisomy 8 associated with a trend for higher age at diagnosis, AML of secondary origin, lower white blood cell counts at diagnosis, worse ELN2017 genetic risk, wild-type NPM1, and mutated IDH1/2 and JAK2. Outcomes after allogeneic HSCT in the entire cohort did not differ between patients with a sole trisomy 8, trisomy 8 with additional cytogenetic aberrations or without a trisomy 8. A trisomy 8 did not affect outcomes within the three ELN2017 risk groups. In accordance with findings in unselected patient cohorts, persistent MRD at allogeneic HSCT in patients with a trisomy 8 identified individuals with a higher risk of relapse following allogeneic HSCT. Conclusions: Outcomes of trisomy 8 patients after allogeneic HSCT did not compare unfavorably to that of other AML patients following allogeneic HSCT. Rather than the presence or absence of a trisomy 8, additional genetic aberrations and MRD at HSCT define outcome differences and aid in informed treatment decisions.

scholarly journals Common points of therapeutic intervention in COVID-19 and in allogeneic hematopoietic stem cell transplantation associated severe cytokine release syndrome

2021 ◽  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Consolidation Therapy ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

AbstractAllogeneic hematopoietic stem cell transplantation (HSCT) and coronavirus disease 2019 (COVID-19) infection can both lead to severe cytokine release syndrome (sCRS) resulting in critical illness and death. In this single institution, preliminary comparative case-series study we compared clinical and laboratory co-variates as well as response to tocilizumab (TCZ)-based therapy of 15 allogeneic-HSCT- and 17 COVID-19-associated sCRS patients. Reaction to a TCZ plus posttransplant cyclophosphamide (PTCY) consolidation therapy in the allogeneic-HSCT-associated sCRS group yielded significantly inferior long-term outcome as compared to TCZ-based therapy in the COVID-19-associated group (P = 0.003). We report that a TCZ followed by consolidation therapy with a Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor given to 4 out of 8 critically ill COVID-19 patients resulted in their complete recovery. Non-selective JAK/STAT inhibitors influencing the action of several cytokines exhibit a broader effect than TCZ alone in calming down sCRS. Serum levels of cytokines and chemokines show similar changes in allogeneic-HSCT- and COVID-19-associated sCRS with marked elevation of interleukin-6 (IL-6), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1) and interferon γ-induced protein 10 kDa (IP-10) levels. In addition, levels of IL-5, IL-10, IL-15 were also elevated in allogeneic-HSCT-associated sCRS. Our multi-cytokine expression data indicate that the pathophysiology of allogeneic-HSCT and COVID-19-associated sCRS are similar therefore the same clinical grading system and TCZ-based treatment approaches can be applied. TCZ with JAK/STAT inhibitor consolidation therapy might be highly effective in COVID-19 sCRS patients.

A Novel Prognostic Factor for Allogeneic Hematopoietic Stem Cell Transplantation Based on Bone Marrow Assessment on the Day of Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3471-3471
Author(s):  
Takahiko Sato ◽  
Naomi Kawashima ◽  
Masafumi Ito ◽  
Yoshiko Atsuta ◽  
Yusuke Kagaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Confidence Interval ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Bone Marrow Aspiration ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract [Introduction] Many factors predicting the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) recipient have been reported so far and widely used to assess the potential risk of undergoing allogeneic HSCT. Residual disease is considered one of the risk factors in HSCT, and mainly evaluated by bone marrow aspiration before HSCT. However, disease statuses at the point of stem cell infusion potentially differ from that of pre-transplant evaluation depending on the sensitivity for conditioning therapy or proliferation speed of the blast. In this study, we assessed residual disease by bone marrow aspiration on the day of stem cell transplantation (called "day 0" of HSCT) in order to analyze the relationship between day 0 marrow statuses and HSCT outcomes. [Methods] This study was designed as a retrospective observational analysis, and we collected the patients who received first allogeneic HSCT for hematological malignant diseases between 2010 and 2014. Extramedullary diseases were excluded from the analysis. All HSCTs were consecutive and performed in our center. Bone marrow aspirated material was examined histopathologically, and residual blasts were evaluated by specific markers by immunostaining. If it has detected residual blasts even if only a few cells, it was defined non complete remission (CR) on day 0 (abbreviated as "non-day0CR"). We divided the patients into two groups according to the existence of residual blast in bone marrow on day 0 of HSCT. [Results] We analyzed 121 HSCT recipients including 35 with acute lymphoblastic leukemia, 3 with acute undifferentiated leukemia, 65 with acute myeloid leukemia, 17 with refractory anemia with excess blasts and 1 with blast phase of chronic myelogenous leukemia. The median follow-up of survivors was 983 days (range 330 - 2092 days), and overall survival (OS) was 72% (95% confidence interval: 63 - 79%) at 1 year after HSCT. In univariate analyses, age higher than median 44 year-old, non-CR at the time of pre-HSCT assessment, hematopoietic cell transplantation specific comorbidity index (HCT-CI) at least 1 point, reduced intensity conditioning, and non-day0CR were extracted as predictors of poor OS. With multivariate analysis, HCT-CI and day 0 marrow status were significantly associated with OS. Furthermore, when patients were limited to pre-transplant non-CR subgroup, the patients achieving complete malignancies-free state on day 0 showed comparable prognosis with those who maintained CR before conditioning (Figure 1). Relapse after allogeneic HSCT was observed in 31 patients, and cumulative incidence of relapse was 11% (95% confidence interval: 6 - 17%) at 1 year after HSCT. With univariate and multivariate analyses, there were significant differences between the patients with CR marrow and those with residual malignancies on day 0 (P = 0.002). There was no significant difference in non-relapse mortality between the two groups (P = 0.18). [Conclusions] We showed that bone marrow status on day 0 was significantly associated with OS and cumulative incidence of relapse. To our knowledge, this is the first report about the association with day 0 marrow status and post-HSCT prognosis. A malignancies-free state on day 0 could predict favorable prognosis in allogeneic HSCT, and the patient with residual malignancies on day 0 had lower OS and higher relapse rate. For the patients with residual malignancies on day 0, rapid tapering of immunosuppressant or arrangement of scheduled donor lymphocyte infusion may improve the outcomes. Disclosures Miyamura: Nippon Shinyaku CO, LT: Honoraria; Pfizer Inc: Honoraria; Novartis Pharmaceutical: Honoraria; Alexion Pharmaceutical Inc: Honoraria.

scholarly journals The Role of Measurable Residual Disease (MRD) in Hematopoietic Stem Cell Transplantation for Hematological Malignancies Focusing on Acute Leukemia

2019 ◽  
Vol 20 (21) ◽  
pp. 5362 ◽  
Author(s):  
Anna Czyz ◽  
Arnon Nagler
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematological Malignancies ◽  
Residual Disease ◽  
Hematopoietic Stem ◽  
Measurable Residual Disease ◽  
Open Issues

The significance of measurable residual disease (MRD) in hematopoietic stem cell transplantation (HSCT) is well recognized in different hematological malignancies, but the evidence indicate that pre-transplant MRD status is of particular importance in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In ALL, inadequate response at the level of MRD is a commonly accepted risk factor for relapse and thus an indication for allogeneic HSCT. Similarly, growing evidence from the literature strongly suggest that MRD detected by multiparameter flow cytometry or molecular techniques should be also used for risk stratification in AML at the time of HSCT. Despite the well-defined association of MRD and outcomes of HSCT in acute leukemias, there are still many open issues such as the role of additional pre-transplant consolidation for MRD eradication, the ability of HSCT to overcome negative influence of MRD positivity on survival, the impact of conditioning regimen intensity on MRD clearance post HSCT, and transplantation outcomes or the selection of optimal donor with regards to MRD status. In addition, the role of MRD assessment in guiding post-transplant maintenance treatment should also be addressed in prospective trials. These open issues mostly awaiting further clinical studies will be discussed in our current review.

scholarly journals Hematopoietic stem cell transplantation for patients with AML in first complete remission

Blood ◽  
2016 ◽  
Vol 127 (1) ◽  
pp. 62-70 ◽  
Author(s):  
Jan J. Cornelissen ◽  
Didier Blaise
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Residual Disease ◽  
Hematopoietic Stem ◽  
Recent Developments ◽  
Postremission Therapy

Abstract Postremission therapy in patients with acute myeloid leukemia (AML) may consist of continuing chemotherapy or transplantation using either autologous or allogeneic stem cells. Patients with favorable subtypes of AML generally receive chemotherapeutic consolidation, although recent studies have also suggested favorable outcome after hematopoietic stem cell transplantation (HSCT). Although allogeneic HSCT (alloHSCT) is considered the preferred type of postremission therapy in poor- and very-poor-risk AML, the place of alloHSCT in intermediate-risk AML is being debated, and autologous HSCT is considered a valuable alternative that may be preferred in patients without minimal residual disease after induction chemotherapy. Here, we review postremission transplantation strategies using either autologous or allogeneic stem cells. Recent developments in the field of alternative donors, including cord blood and haploidentical donors, are highlighted, and we discuss reduced-intensity alloHSCT in older AML recipients who represent the predominant category of patients with AML who have a high risk of relapse in first remission.

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with Recurring Hodgkin’s Lymphoma: An EBMT Study on 151 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3061-3061 ◽  
Author(s):  
Alexander Claviez ◽  
Carmen Canals ◽  
Marc Boogaerts ◽  
Jerry Stein ◽  
Stephen Mackinnon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
The Impact ◽  
Time Point

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients. Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005. Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively. Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.

The Use of Imatinib with Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation Improves Survival of Philadelphia Positive Acute Lymphoblastic Leukemia in Adults

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3653-3653
Author(s):  
Josefina Perez-Nuñez ◽  
Antonio Jimenez-Velasco ◽  
Katy Hurst ◽  
Manuel Barrios-Garcia ◽  
MJ Moreno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Philadelphia positive acute lymphoblastic leukemia (Ph + ALL) accounts for approximately 20% -30% of all adult ALL. The prognosis of patients with Phi + ALL is unfavorable when treated with standard chemotherapy schemes, presenting a long-term survival of 15% -20%. Since the introduction of Imatinib (IM) to treatment regimens the survival of these patients has improved, although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. We conducted a retrospective analysis of Ph + ALL patients before and after IM became available in order to analyze the impact of IM on survival in adult Phi + ALL. Patients and methods Between April 1997 and April 2013 we diagnosed 120 over 15 year old patients with ALL (B and T lineage), 31 (25.8%) of which were Phi +, all B lineage. Of these 31 cases, 30 were treated with protocols from Spanish group PETHEMA with curative intent. 14 of them (47%) were treated with chemotherapy and Imatinib (IM cohort) and 16 (53%) with chemotherapy (pre-IM cohort). In 17 of the 30 cases allogeneic HSCT was performed, 7 in the pre-IM cohort and 10 in the IM cohort. In the post-transplant period, two patients were treated with Dasatinib due to positive minimal residual disease (BCR-ABL1 positive). The probabilities of overall survival (OS) (death) and event free survival (EFS) (no response, relapse or death) were estimated using the Kaplan-Meier product limit method. Differences between groups were tested using the X2 test. Univariate analysis was performed using Cox regression models or log-rank test. Multivariate analysis was performed using Cox proportional hazards regression model. The study was conducted in accordance with the Declaration of Helsinki. Results The median age was 38 years (range, 15-66 years), 17 patients were males and 13 females. The whole series survival was 32.4 ± 9.2%. The OS mean of the pre-IM cohort was 3.1 years (CI 95%, 0.5-5.7) and 6.9 years (CI 95%, 4.4-9.4) in the IM cohort (figure 1). The main characteristics of both groups are reflected in Table 1. When we analyzed the EFS, the variables that influenced it were being treated with IM (48% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.03), having received an allogeneic HSCT (45% versus 8%, p = 0.004) and being in first complete remission before allogeneic HSCT (51% versus 0%, p <0.001). In the analysis of OS, the only variables with prognostic significance were: treatment with IM (63% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.01) and having received an allogeneic HSCT (55 % versus 0%, p <0.001). When the 17 patients that received allogeneic HSCT were analyzed separately, OS in the pre-IM cohort was 29 ± 17% versus 79 ± 13% in the IM cohort (p = 0.057). Table 1. Patient characteristics (N=30) Characteristic Pre-IM cohort(N=16) IM cohort(N=14) P Female/Male 7/9 6/8 0.96 Age ² 40 years 12 (75%) 10 (71%) 0.82 ³ 50 x109/L WBC 8 (50%) 4 (29%) 0.23 Transcript type: e1a2 b2a2/b3a2 12 (75%) 4 (25%) 11 (79%) 3 (21) 0.83 Morphological CR after induction 13/15 (88%) 13/13 (100%) 0.17 No. of Allo-HSCT 7 (44%) 10 (71%) 0.13 CR pre Allo-HSCT: 1CR 2CR 5 (71%) 2 (29%) 10 (100%) 0 (0%) 0.07 Relapse 8/13 (61.5%) 4/13 (31%) 0.12 Exitus 14 (87.5%) 5 (36%) 0.003 Abbreviations: IM, imatinib. WBC, white blood cells. CR, complete remision. Allo-HSCT, allogenetic hematopoietic stem cell transplantation. Figure 1 Figure 1. Conclusions In our study we show how adult Phi + ALL patients who are treated with chemotherapy associated with IM and subsequently receive an allogeneic HSCT exhibit a higher overall survival rate than those treated in the pre-IM era. Although Phi + ALL is still considered of very high risk, in our series of patients treated in the IM era, with a follow-up of over 7 years, overall survival was of 63%, higher than that of historical series of adults with Phi negative ALL. This work has been financed by a grant from the Malaga Association for Research in Leukemia "AMPILE" and the FIS 11-01966 project. Disclosures No relevant conflicts of interest to declare.

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