Ivosidenib (IVO) prior to hematopoietic cell transplant for patients with IDH1-mutant relapsed or refractory acute myeloid leukemia (R/R AML).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7521-7521
Author(s):  
Courtney Denton Dinardo ◽  
Eytan Stein ◽  
Arnaud Pigneux ◽  
Jessica K. Altman ◽  
Robert Collins ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Mononuclear Cells ◽  
Survival Rates ◽  
Digital Pcr ◽  
Hematopoietic Cell ◽  
Study Cohort ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Entire Study

7521 Background: Allogeneic hematopoietic cell transplantation (HCT) provides a potentially curative option for patients (pts) with R/R AML. Disease status at the time of transplant is a major determinant of long-term prognosis, with pts typically receiving salvage chemotherapy prior to HCT to induce a remission. However, older and/or heavily pre-treated pts frequently cannot tolerate intensive chemotherapy (IC) or do not obtain adequate disease control to permit an HCT. IVO is an oral, potent, targeted inhibitor of mutant IDH1 (mIDH1) approved for the treatment of adults with newly diagnosed AML ≥75 y of age or ineligible for IC, and those with R/R AML. We assessed HCT outcomes in pts with m IDH1 R/R AML who proceeded to HCT after treatment with IVO in a phase I study (NCT02074839). Methods: Baseline characteristics, clinical response (including CR, CRi/CRp, MLFS), and overall survival (OS) for the subgroup of pts with m IDH1 R/R AML who received IVO 500 mg QD, responded to treatment and then underwent HCT are reported. m IDH1 variant allele frequency (VAF) from bone marrow mononuclear cells was assessed using BEAMing digital PCR (0.02–0.04% VAF detection limit). Results: Among 179 pts with R/R AML treated with IVO, 18 proceeded to HCT: median age, 61.5 y (range 36–68); 56% male; 16.7% had secondary AML; 27.8% had ≥3 prior regimens; 11.1% had a prior HCT. The median duration of IVO treatment prior to HCT was 3.9 mo (range 2.1–15.2). The last reported response prior to HCT was 50.0% CR. Six- and 12-mo post-HCT survival rates were 77.8% and 50.0%; median relapse-free survival post HCT was 7.3 mo (range 2.6–NE). Median OS from start of IVO was 16.8 mo (95% CI 9.2, NE) for HCT pts vs 9.0 mo (95% CI 7.1, 10.2) in the entire study cohort; median follow-up time, 33.2 mo (range 3.2–41.9). Eight HCT pts were censored for OS: 5 are in remission, 2 relapsed and are in survival follow-up, and 1 was lost to follow-up. Median OS was not estimable (95% CI 9.1, NE) for the 12 HCT pts who achieved CR after IVO therapy and was 20.5 mo (95% CI 16.4, NE) for the 31 CR pts who did not undergo HCT. m IDH1 was undetectable in 1/18 (6%) pts; 4/18 (22%) pts had reduction below 1% VAF in ≥1 at the last assessment prior to HCT. Conclusions: IVO monotherapy is a putative treatment option to induce remissions prior to HCT for m IDH1 R/R AML pts who are not considered candidates for intensive salvage therapy. Post-transplant survival rates are encouraging and warrant further investigation of IVO monotherapy or combination salvage therapies prior to HCT. Clinical trial information: NCT02074839 .

Long-term outcomes of survivors of autologous hematopoietic-cell transplantation for refractory and relapsed Hodgkin’s Disease

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6554-6554
Author(s):  
K. A. Goodman ◽  
V. Serrano ◽  
E. R. Riedel ◽  
S. Gulati ◽  
C. H. Moskowitz ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Risk Of Death ◽  
Increased Risk

6554 Background: With improvements in survival among refractory/relapsed Hodgkin’s Lymphoma (HL) patients after high-dose chemo-radiotherapy and autologous hematopoietic-cell transplant (AHCT), it is important to evaluate risk of late complications in this heavily treated population. Methods: From 1985–1998, 218 refractory/relapsed HL patients were treated on high dose chemo-radiotherapy and AHCT salvage protocols. 153 (70%) surviving ≥2 years after AHCT were analyzed. All received either radiotherapy with initial therapy or total lymphoid irradiation and involved field boost with the conditioning regimen (43%). Information from surviving patients was obtained through a self-administered questionnaire. The NDI was queried to determine vital status and cause of death. Primary endpoint was non-HL mortality, defined as mortality due to cardiac causes, infection or second malignancy (SM). Competing risk methods were used to calculate cause-specific mortality rates and examine its predictors. All events were calculated from 2 years post-AHCT to date of death/last follow-up. Results: Median follow-up time was 11 years. There have been 51 deaths, 32 due to HL and 19 due to other causes. Eleven deaths were due to SM: AML (3), MDS (2), NHL (2), NSCLC (2), gastric and colon cancer. There were 8 non-SM deaths: cardiac toxicity (4), infection, aplastic anemia, suicide, unknown causes (1 each). The 10 and 15-year overall survival (OS) rates are 64% and 57%, respectively. The 10-year cumulative incidence of death from HL and from non-HL causes were 22% and 13.5% ( table ). By univariate analysis, increased risk of death due to SM was associated only with higher age at AHCT (p=0.02). Conclusions: While HL initially accounts for the majority of deaths among patients surviving high-dose therapy, the HL mortality rate plateaus and risk of death from non-HL mortality increases after 5 years. Yet, even at 15-years, SM risk does not exceed that observed in patients treated with standard regimens. [Table: see text] No significant financial relationships to disclose.

scholarly journals Post-Transplant Cyclophosphamide and Tacrolimus—Mycophenolate Mofetil Combination Governs GVHD and Immunosuppression Need, Reducing Late Toxicities in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors

2021 ◽  
Vol 10 (6) ◽  
pp. 1173
Author(s):  
Fabrizio Carnevale-Schianca ◽  
Daniela Caravelli ◽  
Susanna Gallo ◽  
Paolo Becco ◽  
Luca Paruzzo ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

Combined direct antineoplastic activity and the long-lasting immunological effects of allogeneic hematopoietic cell transplant (HCT) can cure many hematological malignancies, but broad adoption requires non-relapse mortality (NRM) rates and graft-versus-host disease (GVHD) control. Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given with tacrolimus/mofetil mycophenolate (T/MMF) showed activity following allogeneic peripheral blood stem cell transplantation (alloPBSCT). Here, we report the experience of a larger cohort (85 consecutive patients) and expanded follow-up period (03/2011–12/2019) with high-risk hematological malignancies who received alloPBSCT from Human-Leukocyte-Antigens HLA-matched unrelated/related donors. GVHD-prophylaxis was PTCy 50 mg/kg (days+3 and +4) combined with T/MMF (day+5 forward). All patients stopped MMF on day+28 with day+110 = median tacrolimus discontinuation. Cumulative incidences were 12% for acute and 7% for chronic GVHD- and no GVHD-attributed deaths. For surviving patients, the 12, 24, and 36-month probabilities of being off immunosuppression were 92, 96, and 96%, respectively. After a 36-month median follow-up, NRM was 4%; median event-free survival (EFS) and overall survival (OS) had yet to occur. One- and two-year chronic GVHD-EFS results were 57% (95% CI, 46–68%) and 53% (95% CI, 45–61%), respectively, with limited late infections and long-term organ toxicities. Disease relapse caused the most treatment failures (38% at 2 years), but low transplant toxicity allowed many patients (14/37, 38%) to receive donor lymphocyte infusions as a post-relapse strategy. We confirmed that PTCy+T/MMF treatment effectively prevented acute and chronic GVHD and limited NRM to unprecedented low rates without loss of disease control efficacy in an expanded patient cohort. This trial is registered at U.S. National Library of Medicine as #NCT02300571.

scholarly journals Inadequate survivorship care after allogeneic hematopoietic cell transplantation: A retrospective chart review

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1389 ◽  
Author(s):  
Sunn Sunn Thaw ◽  
Shernan Holtan ◽  
Qing Cao ◽  
Michael Franklin ◽  
Nyan Paye ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Retrospective Chart Review ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Survivorship Care ◽  
Hematopoietic Cell Transplant ◽  
Organ Systems ◽  
Care Guidelines

Background: Hematopoietic cell transplant (HCT) survivors are at risk of developing long-term complications. Guidelines for survivorship care of HCT recipients were published in 2012; however, the degree to which these guidelines are incorporated into clinical practice is unknown. The purpose of this study was to determine whether providers utilize the 2012 guidelines and analyze whether survivorship-focused providers, provider gender, or provider year of practice influenced adherence to these guidelines. Methods: Adult allogeneic HCT recipient’s medical records were reviewed at the University of Minnesota between 2010 and 2012; only patients who survived without relapse to their 2-year follow-up visit after HCT were included. A semi-quantitative scoring system was developed providing 1 point for each of the 13 organ systems assessed by the 2012 survivorship care guidelines. Data was collected on history, clinical exam, laboratory tests, preventive measures, and counseling. The primary endpoint was the overall score for adherence to the survivorship care guidelines. Wilcoxon rank-sum tests for continuous and Chi-square tests for categorical factors were used to compare the overall score between provider groups (survivorship-focused providers vs others), provider gender, and provider year of practice (≥10 years vs <10 years). Results: Fifteen providers (9 male, 3 survivorship-focused, 7 with <10 years of practice) provided follow-up care to 77 HCT survivors. Survivorship-focused providers had a higher median overall score than other providers (median 10 vs 8, p<0.01).  Female providers had a higher median overall score than male providers (median 9.0 vs 8, p<0.01). There was no difference in median overall score based on provider year of experience (p=0.43). Conclusions: In conclusion, survivorship-focused providers were more likely to achieve long-term screening recommendations. However, even within this group, adherence to the 2012 screening and preventive practice guidelines was incomplete.  Further efforts to automate and standardize the survivorship assessments in HCT survivors are necessary.

scholarly journals Management of Herpesvirus Infections in Hematopoietic Cell Transplant Recipients

2021 ◽  
Vol 2 (1) ◽  
pp. 8-21
Author(s):  
Jan Styczynski
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cellular Therapy ◽  
Hematopoietic Cell ◽  
Host Cells ◽  
Preventive Strategy ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Screening Assay ◽  
Specific Level

Following primary infection, herpesviruses establish latency in infected individuals in the host cells and may reactivate upon external stimuli and during periods of immunosuppression. The objective of this paper was to the present current strategies on preventive and therapeutic management of infections with herpesviruses in recipients of hematopoietic cell transplantation. Strategies of antiviral management include prophylaxis, pre-emptive treatment and targeted treatment. Empirical therapy is not used in antiviral strategies. Prophylaxis can be done at universal (preventive strategy) and specific level. Universal prophylaxis includes non-pharmacologic methods of prevention of infection or reactivation. Risk-adapted specific prophylaxis includes use of specific antivirals or cellular therapy or other specific methods in order to prevent specific infection, in high-risk groups. Pre-emptive therapy means use of therapeutic approaches in asymptomatic infection, detected by a screening assay. Targeted therapy is used in established specific viral end-organ infections. The following sections of the paper refer to prophylaxis and treatment strategies, respectively, against CMV, EBV, HSV, VZV, HHV-6, HHV-7, and HHV-8 after allogeneic hematopoietic cell transplantation.

scholarly journals The Hematopoietic Cell Transplant Comorbidity Index predicts survival after allogeneic transplant for nonmalignant diseases

Blood ◽  
2019 ◽  
Vol 133 (7) ◽  
pp. 754-762 ◽  
Author(s):  
Monica S. Thakar ◽  
Larisa Broglie ◽  
Brent Logan ◽  
Andrew Artz ◽  
Nancy Bunin ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Cox Regression ◽  
Bone Marrow Failure ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Research Database ◽  
Hematopoietic Cell Transplant ◽  
Risk Of Death ◽  
Increased Risk ◽  
Comorbidity Index

Abstract Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases.

Donor T Cells from B Cell Deficient Mice Inhibit B Cell Development in Normal Recipients after Hematopoietic Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3265-3265
Author(s):  
Antonia M.S. Mueller ◽  
Jessica A. Allen ◽  
David Miklos ◽  
Judith A. Shizuru
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Hematopoietic Stem ◽  
Donor Chimerism ◽  
Donor T Cells ◽  
The Impact

Abstract Allogeneic hematopoietic cell transplant (HCT) recipients often exhibit B cell (BC) lymphopenia due, in part, to graft-versus-host-disease (GVHD). Here, we studied the impact of donor T cells (TC) on BC deficiency post minor antigen-mismatched HCT. Following lethal irradiation, BALB.B mice were given FACS purified hematopoietic stem cells (HSC: cKIT+Thy1.1loLin-Sca-1+) alone, with whole splenocytes (SP), CD4 or CD8 TC from minor antigen-mismatched C57BL/6 (B6) mice. Chimerism analyses were performed on day (d) 30, 60, and 90. When pure HSC were transplanted, BCs reconstituted promptly (median 33% of lymphocytes [d30]; 61% [d60]; 74% [d90]), whereas TC engraftment was retarded and did not achieve full donor chimerism. Addition of SP or CD4 TCs, or to a lesser degree CD8 TCs, delayed BC reconstitution, with extremely low percentages of BCs beyond d60. This BC suppression correlated with the degree of acute GVHD, and BC numbers increased with recovery from GVHD. Additionally, this BC suppression was in stark contrast to TC development, with TC transfer resulting in early conversion to full donor chimerism. To test if previous events in the donor sensitize TCs against BC features (e.g. minor antigens), thereby promoting anti-BC cytotoxicity post-HCT, TCs from B6 muMT mice were co-transplanted with HSC. muMT mice are devoid of mature BCs because they lack the mu chain; consequently, their TCs were not exposed to BCs prior to transfer. Remarkably, BC engraftment was completely prevented through d90. TCs regenerated faster, but the vast majority originated from spleen and not HSC. To differentiate this lack of BC engraftment from GVHD-associated, alloreactive BC lymphopenia, syngenic B6 recipients were used. Again, initially complete blockade of BC engraftment was observed, although this suppression was overcome earlier post-HCT as compared to the minor-mismatched pair (median % BC d60: ’HSC only’ recipients 52%; +CD4 17%; +CD8 48%). To clarify if this phenomenon was a purely cytotoxic reaction of muMT TC against BCs, we used WT B6 HSC +/− SP as donors and lethally or sublethally irradiated muMT mice as recipients. All groups, including sublethally irradiated animals, where host muMT TC were still present, engrafted BCs making a direct anti-BC cytotoxicity unlikely as the sole cause of the BC inhibition. FACS analysis of bone marrow was used to assess the developmental stages of BCs (Hardy fractions (Fr.) A-F) and revealed GVHD recipients with peripheral B lymphopenia have a shift of B220+ cells from more mature Fr. D-F to immature Fr. A-C stages and a lower proportion of IgM expressing BC. Recipients of the muMT TCs showed, in addition to a shift to more immature stages, a clear block in BC development with an absent switch to the expression of IgM (stage D to E)(Fig. 1). In conclusion, muMT TCs are capable of blocking BC maturation when transferred into WT mice, suggesting defective TC activity in muMT animals necessary for the co-development of both BCs and TCs. Furthermore, this study provides evidence that mature TCs are capable of interfering with BC regeneration post-HCT. Hence, our HCT combinations using WT and muMT B6 mice provide a powerful tool to study the role of TC function in the process of donor BC development post-HCT.

Spiritual/religious struggle in hematopoietic cell transplant survivors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9573-9573
Author(s):  
Stephen Duane Watkins King ◽  
George Fitchett ◽  
Kenneth I. Pargament ◽  
Do Peterson ◽  
David A. Harrison ◽  
...  
Keyword(s):  
Religious Coping ◽  
Hematopoietic Cell Transplantation ◽  
Religious Affiliation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Variable Model ◽  
Adult Age ◽  
Disease Information ◽  
Negative Religious Coping

9573 Background: Spiritual/religious (SR) struggle (e.g., feeling abandoned or punished by God) has been associated with poorer coping and quality of life (QOL), greater depression and pain, and health declines in general cancer populations. Few studies have been conducted among survivors of hematopoietic cell transplantation (HCT). This study examined the prevalence and predictors of SR struggle in HCT survivors. Methods: Data were collected as part of an annual questionnaire of adult (age >18 years) survivors of HCT at Fred Hutchinson Cancer Research Center in Seattle, WA. The 2011 survey included a SR module that incorporated the following items: Negative Religious Coping subscale of Brief RCOPE, subscales from the McGill QOL Questionnaire and the SF-36, Patient Health Questionnaire-8, disease information and socio-demographics. SR struggle was defined as any non-zero response on the Negative Religious Coping subscale of the Brief RCOPE. A multi-variable logistic regression model was used to determine factors associated with SR struggle. Results: Of 2113 returned surveys (52% response rate), 83% returned the SR module (n=1745) and of those 1586 were included in this analysis. Subjects were 49% female; 67% Christian and 20% Agnostic/Atheist/No preference; and 91% white. Mean age was 55 years; survivors ranged from 6 months to 40 years post-transplant. Primary indications for transplant were leukemia (49%), lymphoma (20%), and multiple myeloma (15%). Twenty-eight percent indicated SR struggle. In a multi-variable model, SR struggle showed statistically significant associations with age >=65 years (odds ratio [OR] .57, p=.02); patient report of being religious only (OR 3.5, p<.001) or spiritual only (OR 1.8, p<.001) compared to being both religious and spiritual; depression (OR 1.1, p<.001); and better social support (OR 0.77, p<.001). Time since HCT, religious affiliation and race/ethnicity did not show statistically significant associations with SR struggle. Conclusions: SR struggle is common among HCT survivors, even years after HCT.Further study is needed to determine causal relations, longitudinal trajectory, impact of struggle intensity, and effects of SR struggle on health, mood and social roles for HCT survivors.

scholarly journals High Survival Rates in Adult Allogenic Hematopoietic Cell Transplant Patients with Adenovirus Viremia Treated with Brincidofovir

2018 ◽  
Vol 24 (3) ◽  
pp. S383-S384 ◽  
Author(s):  
Rocco Richards ◽  
Leslie Cheteyan ◽  
Esperanza B. Papadopoulos ◽  
Ann A. Jakubowski ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
Survival Rates ◽  
Hematopoietic Cell ◽  
High Survival ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Transplant Patients

scholarly journals Steroid-dependent acute GVHD after allogeneic hematopoietic cell transplantation: risk factors and clinical outcomes

2021 ◽  
Vol 5 (5) ◽  
pp. 1352-1359
Author(s):  
Najla El Jurdi ◽  
Ahmad Rayes ◽  
Margaret L. MacMillan ◽  
Shernan G. Holtan ◽  
Todd E. DeFor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Steroid Dependent ◽  
Steroid Sensitive

Abstract Acute graft-versus-host disease (aGVHD) has various risk factors and outcomes. We defined distinct aGVHD treatment response groups based on response to first-line corticosteroids: steroid sensitive (SS), steroid resistant (SR), and the rarely studied steroid dependent (SD) aGVHD. In 1143 consecutive adult and pediatric allogeneic hematopoietic cell transplant recipients, 385 (34%) developed aGVHD, with 10% having SS aGVHD, 9% SD aGVHD, and 14% SR aGVHD. The only factor significantly associated with SD in comparison with SS was older age (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4-11.3, when comparing 18- to 60-year-olds with &lt;18-year-olds). Factors significantly associated with SR in comparison with SS were unrelated donor (OR, 3.0; 95% CI, 1.2-7.4) and Minnesota high-risk aGVHD (OR, 2.4; 95% CI, 1.3-4.6). SR aGVHD was independently associated with higher risk for 2-year overall mortality (hazards ratio [HR], 1.8; 95% CI, 1.2-2.8) and nonrelapse mortality (NRM; HR, 2.1; 95% CI, 1.2-3.9). SS and SD GVHD groups had similar overall survival and NRM. The cumulative incidence of chronic GVHD was highest in the SD group, followed by the SR and SS groups (46%, 41%, and 29%, respectively). SD and SS GVHD had similar prognoses, both markedly better than those of the SR groups.

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