RESUMEN
BACKGROUND: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post-alloHCT outcomes. METHODS: We retrospectively examined 273 alloHCT recipients, 158 in the non-letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV-seropositive and met criteria for high risk of CMV reactivation. RESULTS: Median start of letermovir was 21 days post-alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p < .001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p = .54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p = .69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p = .27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR. CONCLUSIONS: Letermovir prophylaxis started at day +21 post-alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes.
Asunto(s)
Acetatos , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Quinazolinas , Humanos , Citomegalovirus , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Receptores de Trasplantes , Estudios Retrospectivos , Canadá/epidemiología , Antivirales/uso terapéuticoRESUMEN
Letermovir, a novel anti-cytomegalovirus (CMV) agent acts by inhibiting the viral terminase complex and is approved for primary prophylaxis in CMV seropositive patients post allogeneic hematopoietic cell transplantation (HCT). The favorable efficacy and safety profile make it an attractive option for use as secondary prophylaxis in patients at high-risk for CMV reactivation. In this study, we report the efficacy and safety of letermovir secondary prophylaxis after at least one treated episode of CMV reactivation in a cohort of 39 high-risk patients. Thirty two (82%) patients received anti-thymocyte globulin (ATG), 27 (69%) received a combination of ATG and post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis. Twenty one patients (54%) received CMV seronegative grafts. In addition, 18 (46%) patients had HLA mismatched unrelated or haploidentical donors while 18 (46%) had active GVHD requiring immunosuppression at the time of commencing secondary prophylaxis. Letermovir was initiated at a median of 47 days (range, 41-56) after HCT and was administered for a median duration of 77 days (range, 46-90). A single breakthrough CMV reactivation was noted in this high-risk cohort. Four additional episodes of CMV reactivation occurred at a median of 28 days (range, 23-59 days) after discontinuation of secondary prophylaxis. The drug was well tolerated and 77% of the cohort completed the planned duration of secondary prophylaxis. None of the patients discontinued treatment due to treatment-related adverse effects. In conclusion, letermovir is effective and well tolerated and may be considered for secondary prophylaxis in patients at high risk for CMV reactivation. Prospective studies are required to validate these findings.
RESUMEN
Cytomegalovirus (CMV) reactivation post-allogeneic hematopoietic cell transplantation (post-alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre-alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis. CMV serology was assessed at consult and pretransplant. The cohort was divided into four groups based on pretransplant CMV seroconversion: negative to positive (Group 1), positive to negative (Group 2), consistently negative (Group 3), and consistently positive (Group 4). Eighty-nine patients (12%) had seroconverted from negative to positive, 17 (2%) from positive to negative, 151 (20%) were consistently seronegative, and 495 (66%) were consistently seropositive pretransplant. For the four CMV serostatus groups, cumulative incidence of CMV reactivation at 6 months posttransplant was 4.5%, 47.1%, 6.6%, and 76.6% for Groups 1, 2, 3, and 4, respectively (p < .0001). No differences between groups were seen regarding Grade III-IV acute graft-versus-host disease (GVHD) (p = .91), moderate/severe chronic GVHD (p = .41), or graft failure (p = .28). On multivariable analysis, there was no impact of CMV serostatus group on overall survival (p = .67), cumulative incidence of relapse (p = .83) or non-relapse mortality. alloHCT patients who demonstrate CMV seroconversion pretransplant from negative to positive have a very low risk of CMV reactivation posttransplant. The observed seroconversion may be due to passive CMV immunity acquired through blood products. Quantitative CMV immunoglobulin G/immunoglobulin M pretransplant may help differentiate between true seroconversion and passively transmitted CMV immunoglobulin.
RESUMEN
Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HSCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HSCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 33 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other acute myeloid leukemia-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (P=0.969), relapse incidence (P=0.600) or non-relapse mortality (P=0.570). Donor CHIP did not impair neutrophil (P=0.460) or platelet (P=0.250) engraftment, the rates of acute (P=0.490), or chronic graft-versus-host disease (P=0.220). No significant difference was noted for secondary malignancy following HSCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HSCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pretransplant evaluation of donors prior to stem cell donation.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Hematopoyesis Clonal , Estudios de Seguimiento , Trasplante Homólogo/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
Haploidentical donors offer a potentially readily available donor, especially for non-White patients, for hematopoietic cell transplantation (HCT). In this North American collaboration, we retrospectively analyzed outcomes of first HCT using haploidentical donor and post-transplantation cyclophosphamide (PTCy) in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap neoplasms (MDS/MPN). We included 120 consecutive patients who underwent HCT using a haploidentical donor for MDS/MPN across 15 centers. Median age was 62.5 years and 38% were of non-White/Caucasian ethnicity. The median follow-up was 2.4 years. Graft failure was reported in seven of 120 (6%) patients. At 3 years, nonrelapse mortality (NRM) was 25% (95% confidence interval [CI]: 17-34), relapse 27% (95% CI: 18-36), grade 3-4 acute graftversus- host disease 12% (95% CI: 6-18), chronic graft-versus-host disease requiring systemic immunosuppression 14% (95% CI: 7-20), progression-free survival (PFS) 48% (95% CI: 39-59), and overall survival (OS) 56% (95% CI: 47-67). On multivariable analysis, NRM was statistically significantly associated with advancing age at HCT (per decade increment, subdistribution hazard ratio [sdHR] =3.28; 95% CI: 1.30-8.25); relapse with the presence of mutation in EZH2/RUNX1/SETBP1 (sdHR=2.61; 95% CI: 1.06-6.44); PFS with advancing age at HCT (per decade increment, HR=1.98, 95% CI: 1.13-3.45); and OS with advancing age at HCT (per decade increment, HR=2.01; 95% CI: 1.11-3.63) and splenomegaly at HCT/prior splenectomy (HR=2.20; 95% CI: 1.04-4.65). Haploidentical donors are a viable option for HCT in MDS/MPN, especially for those disproportionately represented in the unrelated donor registry. Hence, donor mismatch should not preclude HCT for patients with MDS/MPN, an otherwise incurable malignancy. In addition to patient age, disease-related factors including splenomegaly and high-risk mutations dominate outcomes following HCT.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedades Mielodisplásicas-Mieloproliferativas , Neoplasias , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Esplenomegalia , Trasplante de Células Madre Hematopoyéticas/métodos , Ciclofosfamida , Donante no Emparentado , Enfermedad Aguda , Recurrencia , Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Enfermedades Mielodisplásicas-Mieloproliferativas/terapia , América del Norte , Acondicionamiento Pretrasplante/métodosRESUMEN
The outcomes of allogeneic hematopoietic cell transplantation (HCT) in older patients are not well defined. We retrospectively analyzed the outcomes of 332 patients, with the median age of 65 years (range, 60-76), between 2014 and 2019. We categorized them to 3 age groups (G): G1, 60-65 years (n = 175); G2, > 65-70 years (n = 127); and G3, > 70 years (n = 30). The median length of hospitalization during the initial HCT period was 30 days, with a significant difference when stratified by age (p = 0.049). Overall, 183 (58.7%) patients were re-hospitalized within the first 6 months post HCT, and 60 (21.6%) in the second 6-month period. The 2-year OS was 56% in G1, 53% in G2, and 34% in G3 (p = 0.05). The 2-year event-free survival (EFS) was 54% for G1, 49% for G2, and 31% for G3 (p = 0.04). Non-relapse mortality (NRM) at 2 years was 25% in G1, 36% in G2, and 52% in G3 (p = 0.008). In multivariable analysis, patients aged 60-65 years had significantly better EFS (p = 0.04) and had a trend toward lower NRM (p = 0.05) than those aged > 70 years. Re-admission in the first 6 months post HCT had a significant impact on OS, EFS, and NRM. HCT-specific comorbidity index > 3 had significantly affected NRM. Finally, age had a significant influence on length of hospitalization during HCT. In conclusion, patients aged > 70 years have an inferior EFS and higher NRM. This likely related to higher rate of re-admissions due to infectious complications (84%).
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo , Análisis de Supervivencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante , HospitalizaciónRESUMEN
INTRODUCTION: The literature comparing outcomes between myeloablative (MAC) and reduced intensity conditioning (RIC) for acute myeloid leukemia (AML) is conflicting. METHODS: We retrospectively analyzed 451 patients who underwent allogenic hematopoietic cell transplantation (alloHCT) for AML in complete remission (CR) with either RIC (n = 331) or MAC (n = 120) with the use of dual T-cell depletion as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Univariate analysis demonstrated nonrelapse mortality (NRM) at 2 years was 19.1% for MAC and 22.5% for RIC (p = .44). Two-year cumulative incidence of relapse (CIR) was 19.8% for MAC and 24.5% for RIC (p = .15). Two-year overall survival (OS) was 61% and 53% for MAC and RIC, respectively (p = .02). Two-year graft-versus-host disease relapse-free survival (GRFS) was 40.8% for MAC and 33.7% for RIC (p = .30). A propensity score-matched analysis was done matching patients for age, HLA match, in vivo T-cell depletion, and Disease Risk Index (DRI). Two-year OS was 67% for MAC, 66% for RIC (p = .95). A subgroup analysis identified that matched related donor transplants benefit from MAC with OS at 2 years 82.6% versus 57.3% for RIC (p = .006). CONCLUSIONS: In the matched-related donor setting, MAC regimens may offer superior survival. Overall, for our cohort of predominantly in vivo T-cell depleted patients the outcomes of MAC and RIC were similar.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Inducción de Remisión , Recurrencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
BACKGROUND: Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported. METHODS: We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019. Patients with any documented cytogenetic abnormalities were excluded. Targeted next generation sequencing (NGS) was performed in all patients. Baseline characteristics, mutation profile, and outcomes were compared between patients with normal cytogenetics(NC) and those with IC. RESULTS: Sixty-one patients (males 39.3%; median age 59 years) had IC at diagnosis. The proportion of patients with mutations in genes with proven prognostic impact were not different between AML patients with IC and NC. AML patients with NC were more likely to harbor the prognostically favorable NPM1mut /FLT3-ITDwt mutational combination conferring "favorable" risk status. As a result, a larger proportion of patients in the IC group underwent allogeneic hematopoietic stem cell transplantation (allo HCT; 54.1% vs. 39.6%; p = .02). The 2-year RFS (55.9% vs. 58.5%; p = .29) and OS (61.9% vs. 66.9%; p = .48) were similar in IC and NC patients. There was no difference in survival of patients who underwent allo HCT when compared with patients who did not (p = .99). CONCLUSIONS: Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Masculino , Humanos , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Nucleofosmina , Mutación , Pronóstico , Análisis Citogenético , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
BACKGROUND: Pre-transplant pulmonary function testing (PFT) is essential before allogeneic hematopoietic stem cell transplant (HCT), yet the optimal cutoff value for affecting transplant outcomes remains poorly defined. STUDY DESIGN: Retrospective analysis of pre-HCT PFT data from 605 consecutive patients at the Princess Margaret Cancer Centre between January 1, 2004 and December 31, 2013 used binary recursive partitioning to identify cutoff values for overall survival (OS) as an endpoint of transplant outcomes. These values were compared to HCT comorbidity index (HCT-CI) FEV1 cutoffs for OS, cumulative incidence of relapse and non-relapse mortality. RESULTS: FEV1 ≥ 81% was the identified cutoff point. The OS rate at 3 years showed 49.8% (FEV1 ≥ 81%) vs. 36.6% (<81%, p < .001). For HCT-CI cutoffs, the OS rate at 3 years for FEV1 ≥ 80%, 66%-80% and ≤65% were 49.0%, 38.1% and 37.6% (p = .011), respectively. Multivariate analysis confirmed that FEV1 ≥ 81% predicted reduced mortality (HR 0.682, p = .001). Subgroup analysis showed both FEV1 ≥ 81% and FEV1 by HCT-CI cutoffs may stratify patients according to OS and NRM risk in subgroups receiving myeloablative, but not reduced intensity conditioning. CONCLUSION: FEV1 ≥ 81% can predict OS and NRM in our cohort and is potentially simpler when risk stratifying patients undergoing allogeneic HCT, particularly those receiving myeloablative conditioning.
RESUMEN
OBJECTIVE: Cancer caregiving can result in increased psychosocial distress and poor health-related quality of life (QOL). Psychoeducation has been shown to be effective in enhancing caregiving-oriented outcomes. A systematic assessment of the overall effect of psychoeducational intervention (PEI) and identification of individual intervention characteristics that may contribute to the effectiveness of PEI is needed. METHODS: For this meta-analysis, relevant articles were identified through electronic databases using key search terms and their medical subject heading such as "family caregiver," "cancer," and "psychoeducational intervention." RESULTS: Twenty-eight controlled trials with 3876 participants were included. PEIs had beneficial effect on depression (Standardized Mean Difference [SMD] -0.26; 95% CI = -0.50 to -0.01, p < 0.04), anxiety (SMD -0.41; 95% CI = -0.82 to 0.01, p < 0.05), caregiver burden (SMD -0.84; 95% CI = -1.22 to -0.46, p < 0.0001) and QOL (SMD 0.59, 95% CI 0.24-0.93; p < 0.0009) at the immediate post-intervention period. At longer-term follow-up, the effectiveness of PEI was maintained on QOL (SMD 0.39, 95% CI = -0.00 to -0.77, p < 0.05), and anxiety (SMD -0.57; 95% CI = -1.09 to -0.06, p < 0.03). Moderation analysis showed that intervention characteristics such as studies conducted in high-income countries, group intervention and studies that focused on specific and mixed cancers explain some of the high variations observed among the included studies. CONCLUSIONS: PEI may benefit caregivers of cancer patients through the significant effects on caregiver burden, QOL, anxiety, and depression. The findings from the moderation analysis may be important for the design of future interventions.
Asunto(s)
Neoplasias , Calidad de Vida , Humanos , Adulto , Cuidadores/psicología , Sistemas de Apoyo Psicosocial , Depresión/terapia , Depresión/psicología , Neoplasias/terapia , Neoplasias/psicologíaRESUMEN
INTRODUCTION: Prediction of outcomes following allogeneic hematopoietic cell transplantation (HCT) remains a major challenge. Machine learning (ML) is a computational procedure that may facilitate the generation of HCT prediction models. We sought to investigate the prognostic potential of multiple ML algorithms when applied to a large single-center allogeneic HCT database. METHODS: Our registry included 2697 patients that underwent allogeneic HCT from January 1976 to December 2017, 45 pre-transplant baseline variables were included in the predictive assessment of each ML algorithm on overall survival (OS) as determined by area under the curve (AUC). Pre-transplant variables used in the EBMT machine learning study (Shouval et al, 2015) were used as a benchmark for comparison. RESULTS: On the entire dataset, the random forest (RF) algorithm performed best (AUC 0.71±0.04) compared to the second-best model, logistic regression (LR) (AUC=0.69±0.04) (p<0.001). Both algorithms demonstrated improved AUC scores using all 45 variables compared to the limited variables examined by the EBMT study. Survival at 100 days post-HCT using RF on the full dataset discriminated patients into different prognostic groups with different 2-year OS (p<0.0001). We then examined the ML methods that allow for significant individual variable identification, including LR and RF, and identified matched related donors (HR=0.49, p<0.0001), increasing TBI dose (HR=1.60, p=0.006), increasing recipient age (HR=1.92, p<0.0001), higher baseline Hb (HR=0.59, p=0.0002) and increased baseline FEV1 (HR=0.73, p=0.02), among others. CONCLUSION: The application of multiple ML techniques on single center allogeneic HCT databases warrants further investigation and may provide a useful tool to identify variables with prognostic potential.
RESUMEN
PURPOSE: Allogeneic stem cell transplant (allo-HSCT) patients are at risk of malnutrition and weight loss from impaired oral intake resulting from gastrointestinal toxicities, dysgeusia, and psychological effects. METHODS: A retrospective review of 264 adult patients transplanted at Princess Margaret Cancer Centre who achieved relapse-free survival up to 3 months after allo-HSCT was performed. RESULTS: Overall incidence of patients who experienced WL (WL) ≥ 10% from HSCT to 3-month post-transplant was 45.9% and from HSCT to 6 months was 56.6%. Patients with ≥ 10% WL from allo-HSCT at 3 months and 6 months had similar 2-year overall survival (OS) compared to those with < 10% WL, 55.7% vs 62.8% (HR = 1.38, p = 0.11) and 71.1% vs 77.2% (HR = 1.37, p = 0.27), respectively. Patients with ≥ 10% WL 3 and 6 months from allo-HSCT also had similar 2-year relapse-free survival (RFS) compared to those with < 10% WL, 48.1% vs 55.8% (HR = 1.26, p = 0.22), and 62.7% vs 69.8% (HR = 1.29, p = 0.31), respectively. The 2-year transplant-related mortality (TRM) was higher for those with ≥ 10% WL from allo-HSCT to 3 months, 35.4% vs 16.9% (HR = 2.39, p = 0.0007) and 6 months, 22% vs 8% (HR = 3.1, p = 0.0034). Although statistical significance was not observed for OS or RFS, patients who experienced ≥ 10% WL 3- and 6-months post allo-HSCT experienced higher 2-year TRM. These results highlight the importance of early intervention and close monitoring of weight post allo-HSCT. CONCLUSION: Approaches to WL post allo-HSCT should be multifaceted and include members of the interdisciplinary team in order to decrease TRM.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Desnutrición , Adulto , Humanos , Disgeusia , Trasplante de Células Madre , Pérdida de Peso , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
In donor selection for allogeneic stem cell transplant, several factors are considered for potential impact on transplant outcome. Previous publications suggested single HLA-mismatched unrelated donors (MMUD) may be equivalent to 10/10 matched unrelated donors (MUDs). We retrospectively examined factors affecting outcome in a single-center study using ATG followed by post-transplant cyclophosphamide, termed ATG-PTCy, GvHD prophylaxis. Fifty-two patients who received grafts from MMUD and 188 patients transplanted from MUD between January 2015 and December 2019, at Princess Margaret Cancer Centre, Canada, were enrolled. All patients received reduced-intensity conditioning. Overall survival for 9/10 recipients at 2 years was significantly worse, 37.2% versus 68.5% for 10/10 MUDs, p < .001, as were NRM at 1 year 39.5% versus 11.7%, p < .001, and GRFS at 2 years 29.8% versus 58.8%, p < .001, respectively, potentially due to higher incidence of infections including CMV. By multivariable analysis, factors correlating with survival negatively were DRI, and MMUD, whereas for NRM MMUD and increasing age were unfavorable. For GRFS significant unfavorable factors included donor age ≤32 years, female donor to male recipient, DRI high-very high and MMUD. These data suggest that MMUD, primarily HLA-A and HLA-B MMUD, confer significantly inferior outcome despite use of ATG-PTCy. Further development of novel conditioning regimens and GvHD prophylaxis is needed to mitigate these risks.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Suero Antilinfocítico/uso terapéutico , Ciclofosfamida/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA-A , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Donante no EmparentadoRESUMEN
During 2020, the concurrent novel COVID-19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft-versus-host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched-related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post-HSCT, possibly due to the combination of ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Criopreservación/métodos , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/citología , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Anciano , COVID-19/epidemiología , Femenino , Enfermedad Injerto contra Huésped , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Increasing survival of patients with multiple myeloma (MM) has resulted in an increased recognition of therapy-related hematological malignancies (t-MDS/AML, t-ALL, and t-CMML). There are limited data on the role of allogeneic hematopoietic stem cell transplantation (HCT) in this patient population. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent HCT for t-MDS/AML, t-ALL, and t-CMML developing after receiving treatment for MM at our center. Patients were analyzed for myeloma characteristics and therapy, time to diagnosis of therapy-related hematological neoplasms, clinical, laboratory characteristics, transplant details, relapse-free survival (RFS), and overall survival (OS). RESULTS: Twenty patients underwent HCT for therapy-related hematological malignancies after MM (t-MDS/AML = 13, t-ALL = 6, t-CMML = 1). Median(range) age at time of transplant was 62.5 (49-73) years and 70% (n = 14) were male. The most common cytogenetic abnormality was complex/monosomal karyotype in 30% (n = 6) followed by monosomy/deletion of chromosome 5 or 7 in 15% (n = 3) of patients each. Donors were human leukocyte antigen matched (10/10 or 6/6) siblings in 30% (n = 6), unrelated in 60% (n = 12) and haploidentical in 10% (n = 2) patients. Estimated 2-year OS and RFS for the whole cohort were 53.1% and 47.2% respectively. There was a trend toward better survival in patients with t-ALL when compared to t-MDS/AML; however, the difference was not statistically significant. We did not find any pre-transplant or post-transplant factors that were predictive of survival outcomes after multivariate analysis. CONCLUSIONS: Allogeneic HCT provides substantial long-term disease-free survival in a proportion of patients with MM-associated therapy-related hematological malignancies. Multicenter studies with more patients and longer follow-up may provide additional information about factors affecting outcomes.
Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Mieloma Múltiple , Neoplasias Primarias Secundarias , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Femenino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/etiología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/etiología , Mieloma Múltiple/terapia , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodosRESUMEN
INTRODUCTION: Evidence is emerging to support an association between certain human leukocyte antigen (HLA) alleles and the risk of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplant (allo-HSCT). The primary aim of this study was to identify HLA alleles associated with resistance or susceptibility to CMV reactivation. METHODS: We studied 586 adults who underwent allo-HSCT for high-risk hematological malignancies. High-resolution HLA typing data were available for recipients and donors. HLA class I and II alleles observed at a frequency of >5% in our population were included in the analysis. A CMV viremia level of more than 200 IU/ml on weekly monitoring was considered to be indicative of CMV reactivation. RESULTS: The median follow-up time in surviving patients was 21 months (range 4-74 months). The cumulative incidence of CMV reactivation at 6 months in the entire cohort was 55% (95% confidence interval [CI] 50.8%-59.2%). Mismatched donors, increasing recipient age, occurrence of acute graft versus host disease and recipient CMV seropositivity were associated with an increased risk of CMV reactivation. HLA B*07:02 (hazard ratio 0.59, 95% CI 0.40-0.83) was associated with a decreased risk of CMV reactivation. Patients who developed CMV reactivation had a lower incidence of relapse, higher transplant-related mortality (TRM) and lower overall survival (OS) than those without CMV reactivation. There was an adverse correlation of OS and TRM with increasing numbers of CMV reactivations. CONCLUSION: We observed that HLA B*07:02 was associated with a decreased risk of CMV reactivation. CMV reactivation was associated with lower relapse post-transplant, but this did not translate into a survival benefit due to higher TRM.
Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Adulto , Alelos , Citomegalovirus , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Recurrencia Local de Neoplasia , Estudios RetrospectivosRESUMEN
INTRODUCTION: Patients admitted for allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discharged with multiple new medications. At our institution, a new patient Self Medication Program (SMP) was implemented on the allo-HSCT units. An SMP allows patients to practice self-administration of medications in a controlled environment before discharge. We assessed the impact of the SMP on patient medication knowledge, self-efficacy, adherence, and safety. Patient and staff satisfaction with the SMP was also explored. METHODS: Participants in the SMP group received medication counseling by a pharmacist and self-managed their medications with nursing supervision until discharge. Participants in the pre-SMP group received medication counseling by a pharmacist at discharge. All participants completed a Medication Knowledge and Self-Efficacy Questionnaire before discharge and at follow-up. Safety endpoints were assessed for SMP participants. RESULTS: Twenty-six patients in the pre-SMP group and 25 patients in the SMP group completed both questionnaires. Median knowledge scores in the pre-SMP group versus the SMP group were 8.5/10 versus 10/10 at discharge (p = 0.0023) and 9/10 versus 10/10 at follow-up (p = 0.047). Median self-efficacy scores were 38/39 in the pre-SMP group versus 39/39 in the SMP group at both discharge and follow-up (pdischarge = 0.11, pfollow-up = 0.10). The SMP was associated with at least 1 medication event in 7 participants, but no medication incidents. Patient and staff surveys showed a positive perceived value of the SMP. CONCLUSION: Our results demonstrate that the SMP is associated with durable, improved medication knowledge, a trend towards improved self-efficacy, and largely positive perceptions among both staff and patient participants.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Automedicación , Humanos , Autoadministración/psicología , Alta del Paciente , HospitalizaciónRESUMEN
Allogeneic hematopoietic stem cell transplantation (HCT) is associated with significant morbidity and mortality. Elevated pre-transplant ferritin level (ferritinPre-HCT) is reported to be associated with increased mortality following HCT. The present study attempted to determine whether post-transplant ferritin level (ferritinPost-HCT) is associated with outcomes post-HCT, especially in the subgroups which developed acute or chronic graft-versus-host disease (GVHD). Out of 229 patients with serum ferritin level measured post-HCT, median ferritinPost-HCT was 2178 ng/mL. Patients were stratified into low- or high-risk groups using recursive partitioning, based on ferritinPost-HCT (≤ 3169 vs > 3169 ng/mL) and ferritinPre-HCT (≤ 669 vs > 669 ng/mL). Compared to the low ferritinPost-HCT group, the high ferritinPost-HCT group had lower 3-year overall survival (OS) (40.0% vs 66.7%, p < 0.001) and higher non-relapse mortality (NRM) (48.6% vs 17.8%, p < 0.001), but no difference in relapse (10.5% vs 19.7%, p = 0.079). Multivariate analysis confirmed ferritinPost-HCT as an independent prognostic factor for OS (p = 0.001, HR = 2.323) and NRM (p < 0.001, HR = 3.905). However, ferritinPre-HCT did not stratify well for OS or NRM. FerritinPost-HCT was also found to be an independent prognostic marker for OS and NRM in the subgroups which developed GVHD. In our cohort, high ferritinPost-HCT levels were significantly associated with decreased OS and increased NRM independent of ferritinPre-HCT or GVHD. Additional studies including larger sample sizes and prospective investigation are warranted to clarify the prognostic significance and pathophysiology of pre- and post-transplant hyperferritinemia.
Asunto(s)
Ferritinas/sangre , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Ferritinas/análisis , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Avascular necrosis (AVN) is a debilitating complication of allogeneic hematopoietic cell transplantation (HCT). A retrospective review of 845 patients who underwent HCT was conducted. Cumulative incidence of AVN was 6.3% at 4 years. The following risk factors were significantly associated with AVN risk on univariate analysis: age < 45 (p=0.004), moderate to severe chronic GvHD (p<0.001), reduced intensity conditioning (p=0.02), and a diagnosis of acute leukemia (p=0.045). Multivariate analysis confirmed two risk factors: younger age (<45 years), 9.0% vs 4.4% (p=0.011, hazard ratio (HR) 2.134), and moderate-severe chronic GvHD, 15.4% vs 2.1% (p<0.001, HR 4.950). A risk score model was generated assigning a score to each risk factor. A score of 1 was assigned to moderate-severe GvHD or those with age <45. Total score was calculated, thus dividing patient into three groups: low (score 0, n=349, 41.3%), intermediate (score 1, n=379, 44.9%), and high risk (score 2; n=116, 13.7%). This risk score could stratify the patients according to AVN risk (p<0.001). The risk of AVN was 1.5% in the low risk, 6.2% in the intermediate risk, and 20.8% in the high risk groups. Moderate-severe chronic GvHD and younger age (<45 years) are key risk factors for AVN following allogeneic HCT.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Osteonecrosis/etiología , Adulto , Factores de Edad , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/complicaciones , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversosRESUMEN
INTRODUCTION: Recent advances in allogeneic hematopoietic stem cell transplant (HSCT) have allowed us to offer HSCT to older, advanced disease patients with more co-morbidities. Cardiovascular toxicity post-transplant is a major concern due to the increased risk of mortality. Few studies have examined the prevalence of CV events including CAD (MI, angina, PCI, CABG, CHF, arrhythmias), HTN, stroke/TIA, and death in the first 100 days post-transplant. PATIENTS: We assessed the impact of pretransplant MUGA results in predicting postallogeneic HSCT CV events and overall survival in the first 100 days, and whether or not transient anthracycline-induced cardiomyopathy or cumulative anthracycline dose affected overall survival. This retrospective, cohort study included 665 patients with a median age of 52 years who underwent HSCT from 2009 to 2015. RESULTS: The most frequent CV event in the first 100 days post-HSCT was arrhythmia seen in 2.9% of patients followed up by CHF (12.3%), MI (9%), and angina (8%). Two patients had PCI, and both survived the first 100 days. Cardiovascular risk factors predict for a poor MUGA scan but not survival. Higher dose anthracycline pretransplant predicted for a poor outcome. CONCLUSION: A history of CV disease, MI, or CAD was the most important predictive of CV events, P-value = .00002. 88.6% survived the first 100 days. Patients with an EF < 50% had a significant likelihood of having a CV event compared to patients with an EF > 60% (OR = 5.3, 95% CI [1.6-18.1], P = .0219). Cumulative anthracycline dose did not have a significant impact on overall survival.