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Ciclofosfamida , Enfermedad Injerto contra Huésped , Donante no Emparentado , Humanos , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Adulto , Trasplante Haploidéntico/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Anciano , AdolescenteRESUMEN
Involvement of lower gastrointestinal tract (LGI) occurs in 60% of patients with graft-versus-host-disease (GVHD). Complement components C3 and C5 are involved in GVHD pathogenesis. In this phase 2a study, we evaluated the safety and efficacy of ALXN1007, a monoclonal antibody against C5a, in patients with newly diagnosed LGI acute GVHD receiving concomitant corticosteroid. Twenty-five patients were enrolled; one was excluded from the efficacy analysis based upon negative biopsy. Most patients (16/25, 64%) had acute leukemia; 52% (13/25) had an HLA-matched unrelated donor; and 68% (17/25) received myeloablative conditioning. Half the patients (12/24) had a high biomarker profile, Ann Arbor score 3; 42% (10/24) had high-risk GVHD per Minnesota classification. Day-28 overall response was 58% (13/24 complete response, 1/24 partial response), and 63% by Day-56 (all complete responses). Day-28 overall response was 50% (5/10) in Minnesota high-risk and 42% (5/12) in high-risk Ann Arbor patients, increasing to 58% (7/12) by Day-56. Non-relapse mortality at 6-months was 24% (95% CI 11-53). The most common treatment-related adverse event was infection (6/25, 24%). Neither baseline complement levels (except for C5), activity, nor inhibition of C5a with ALXN1007 correlated with GVHD severity or responses. Further studies are needed to evaluate the role of complement inhibition in GVHD treatment.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Inactivadores del Complemento/uso terapéutico , Complemento C5a/uso terapéutico , Estudios Prospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Tracto Gastrointestinal Inferior/patologíaRESUMEN
Total-body irradiation (TBI)-based conditioning regimen is preferred in acute lymphoblastic leukemia (ALL). We retrospectively evaluated allogeneic stem cell transplant (alloSCT) outcomes of 86 adult ALL patients in complete remission (CR) who received TBI-containing reduced intensity (RIC) (Flu/Mel/TBI = 31) and myeloablative conditioning (MAC) (VP16/TBI = 47; CY/TBI = 8) between January 2005 and December 2019. All patients received peripheral blood allografts. Patients in the RIC group were older than the MAC group (61 years old versus 36 years, p < .001). Donor was 8/8 HLA-matched in 83% and unrelated in 65% of patients. Three-year survival was 56.04% for RIC and 69.9% for MAC (HR 0.64; p = .19). Propensity score-based multivariable Cox analyses (PSCA) did not demonstrate any difference in grade III-IV acute graft versus host disease (GVHD) (SHR 1.23, p = .91), chronic GVHD (SHR 0.92, p = .88), survival (HR 0.94, p = .92), and relapse-free survival (HR 0.66, p = .47) between both groups, while relapse rate was lower (SHR 0.21, p = .02) for MAC compared to RIC. Our study did not demonstrate any difference in survival for TBI-containing RIC and MAC alloSCT for adult ALL in CR.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Células Madre , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Inducción de Remisión , Enfermedad Aguda , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento PretrasplanteRESUMEN
The use of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has resulted in reductions in GVHD and improved outcomes in allogeneic hematopoietic cell transplantation (HCT) using HLA-mismatched related donors. We report the 3-year outcomes of the first multicenter prospective clinical trial using PTCy in the setting of mismatched unrelated donor (MMUD) bone marrow HCT. The study enrolled 80 patients, treated with either myeloablative conditioning (MAC; n = 40) or reduced-intensity conditioning (RIC; n = 40), with the primary endpoint of 1-year overall survival (OS). The median follow-up for this study was 34 months (range, 12 to 46 months) in the RIC group and 36 months (range, 18 to 49 months) in the MAC group. Three-year OS and nonrelapse mortality were 70% and 15%, respectively, in the RIC group and 62% and 10% in the MAC group. No GVHD was reported after 1 year. The incidence of relapse was 29% in the RIC group and 51% in the MAC group. OS did not differ based on HLA match grade (63% in the 7/8 strata and 71% in the 4 to 6/8 strata). These encouraging outcomes, which were sustained for 3 years post-HCT, support the continued exploration of MMUD HCT using a PTCy platform. Important future areas to address include relapse reduction and furthering our understanding of optimal donor selection based on HLA and non-HLA factors.
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Médula Ósea , Enfermedad Injerto contra Huésped , Humanos , Estudios de Seguimiento , Estudios Prospectivos , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Donante no Emparentado , RecurrenciaRESUMEN
Mantle cell lymphoma is a rare subtype of non-Hodgkin's lymphoma with poor prognosis and continue to be challenging to treat. The choice of first line induction regimen remains a topic of debate due paucity of clinical trials. We retrospectively evaluated 66 patients diagnosed with mantle cell lymphoma who achieved first complete response after induction chemotherapy followed by autologous stem cell transplant. Treatment groups were divided into low-intensity versus high-intensity regimens. Our data showed the intensity of induction regimen does not impact posttransplant outcomes of mantle cell lymphoma who underwent autologous stem cell transplant in first complete response.
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/terapia , Trasplante Autólogo , Quimioterapia de Inducción , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inducción de Remisión , Trasplante de Células MadreRESUMEN
Purpose: Women with locally advanced/high-risk triple-negative breast cancer treated with the current standard chemotherapy continue to have a poor prognosis. High-dose chemotherapy with autologous stem cell transplant as treatment for locally advanced/high-risk breast cancer remains controversial due to a lack of survival benefit seen in previous phase III trials. However, these trials evaluated a heterogeneous group of patients with different receptor subtypes. A marginal benefit was observed in certain subgroups. We report long-term outcomes of women with stage IIB or III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant at our institution between 1995 and 2001. Methods: This is a retrospective analysis of stage IIB or stage III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant. We excluded women with hormone-positive, HER2/neu-positive/unknown, and/or metastatic disease prior to transplant as per updated AJCC 7th edition guidelines. Patients underwent surgery and either neoadjuvant or adjuvant anthracycline and taxane-based chemotherapy and then proceeded to high-dose chemotherapy and autologous stem cell transplant using carmustine 600 mg/sqm, cyclophosphamide 5.6gm/sqm, and cisplatin 165 mg/sqm (STAMP 1 regimen) for consolidation. This was followed by locoregional breast and lymph node radiation per standard of care. Results: Twenty-nine women (2 stage IIB and 27 stage III) were evaluated. The median age at diagnosis was 43 years (IQR: 40, 51). Eleven patients had 4-9 regional lymph nodes (LN) involved and 16 had 10+ involved LNs. Four patients had T4 or inflammatory breast cancer and two had ipsilateral supraclavicular LNs involved. The median follow-up time is 16 years (95% CI: 12, 19, range <1-19 y) posttransplant. The median overall survival was 15 years (95% CI: 3, 19); the median DFS was 14 years (95% CI: 1, 19). Conclusions: This study of locally advanced/high-risk triple-negative breast cancer treated with adjuvant high-dose chemotherapy and autologous stem cell transplant reveals high overall survival rate. With the current improvement in treatment-related mortality, re-evaluating this approach in this subset of high-risk breast cancer in prospective randomized studies may be worthwhile.
RESUMEN
Utilization of novel agents such as brentuximab vedotin (BV) and check-point inhibitors (CI) has increased in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL). We conducted a retrospective study of 209 patients who had ASCT for r/r cHL at our institution and compared outcomes of those who had ASCT from 2010-2018 (cohort 2, n = 110) with those who had ASCT between 2000 and 2009 (cohort 1, n = 99). The median OS was 7.6 years for cohort 1 [HR 2.08; 95% CI 1.14-3.80; p = 0.017] and not reached for cohort 2; with 4-year improved OS difference of 15% (80% vs 65%) in cohort 2 vs cohort 1. The median PFS of cohort 1 was 30 months vs 39 months for cohort 2[HR 1.24; 95% CI 0.82-1.88; p = 0.3]. This study highlights improved OS of r/r cHL patients who have received ASCT in the novel agent era due to the exposure to agents such as BV and CIs.
Asunto(s)
Enfermedad de Hodgkin , Inmunoconjugados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina , Enfermedad de Hodgkin/patología , Humanos , Inmunoconjugados/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
Limited information is available on the efficacy of post-transplantation cyclophosphamide (PTcy) or thymoglobulin for graft-versus-host disease (GVHD) prophylaxis in mismatched unrelated donor (MMUD) transplants. We retrospectively compared outcomes of 76 adult patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who underwent 7/8 HLA-MMUD transplantation and received either PTcy (50 mg/kg on day 3 and 4) or thymoglobulin (total dose 4.5 mg/kg) for GVHD prophylaxis. In addition, tacrolimus and mycophenolate were used in both groups. Propensity score-based multivariable analyses (PSCA) were performed to adjust confounding effects of patient characteristics between both groups. Between January 2006 and June 2019, 25 patients received PTcy, and 51 received thymoglobulin. Median age of the population was 57 years, 78% of patients had AML, most common graft source was peripheral blood (96%), and 46% received myeloablative conditioning regimens. Median time to neutrophil (15 versus 11 days, P < .001) and platelet engraftment (21 versus 15 days, P = .002) was prolonged in the PTcy group. The cumulative incidence of grade III-IV acute GVHD at day 100 was similar (12% versus 19.6%, P = .38), whereas chronic GVHD at 1 year was lower with PTcy compared to thymoglobulin (16% versus 49%, P = .006). Using PSCA, no difference in survival, relapse, relapse-free survival, and GVHD-free relapse-free survival was seen between groups. However, thymoglobulin was associated with higher incidence of acute (hazard ratio [HR] = 2.63, P = .01) and chronic GVHD (HR = 4.43, P = .03), and non-relapse mortality (HR 3.38, P = .04) compared to PTcy. Our study demonstrated that PTcy resulted in significantly lower rates of acute and chronic GVHD and non-relapse mortality compared to thymoglobulin in 7/8 HLA-MMUD transplants for AML and MDS.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Adulto , Suero Antilinfocítico , Ciclofosfamida/uso terapéutico , Humanos , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Estudios Retrospectivos , Donante no EmparentadoRESUMEN
Fludarabine 30 mg/m2/d × 5 and melphalan 140 mg/m2 × 1 (Flu-Mel140) is a commonly used reduced-intensity conditioning regimen. We hypothesized that addition of 200cGy total body irradiation (TBI) to Flu-Mel140 may improve antitumor activity and transplant outcomes. Primary objectives was overall survival (OS) at 3 years. Secondary objectives were to assess the cumulative incidences of acute and chronic GVHD, relapse-free survival (RFS), relapse rate, and nonrelapse mortality (NRM). We retrospectively evaluated outcomes of patients receiving Flu-Mel140-TBI followed by HLA-matched donor allogeneic hematopoietic stem cell transplantation (alloSCT) using peripheral blood stem cells. Eighty-one patients (median age, 58 years) underwent alloSCT between January 2008 and December 2018. Thirty-one percent of patients had a prior transplant, 32% had high or very-high disease risk index, and the donor was unrelated in 70% of patients. Grade 3 to 4 regimen-related toxicities were mucositis (37%), cardiac toxicity (17%), and renal toxicity (10%). The cumulative incidence of grade III to IV acute GVHD at day +100 was 24.7% and chronic GVHD at 1 year was 51.3%. Median follow-up for survival was 6.1 years. At 3 years, OS was 39.81%, RFS was 31.47%, and relapse rate was 30.5%. One-year NRM was 29.9%. Patients undergoing first transplantation experienced improved OS compared with second or beyond (63.08% versus 42.31%, P = .02). After adjusting for disease subtypes, age (≤55 versus 55), comorbidity index (CI), number of transplant and GVHD prophylaxis, multivariable analysis did not demonstrate any survival difference among disease subtypes. High CI (≥3) was predictive of adverse OS and NRM, whereas older age (>55 years) was associated with high NRM. Our study shows that Flu-Mel140-TBI seems feasible and provides durable disease control. Addition of TBI did not appear to improve outcomes compared to previously published reports of Flu-Mel140. Considerable NRM could result from the inclusion of patients with older age and prior transplants.
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Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Anciano , Humanos , Melfalán , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Vidarabina/análogos & derivados , Irradiación Corporal TotalRESUMEN
PURPOSE: Hematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT. PATIENTS AND METHODS: We performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy. RESULTS: Notably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS. CONCLUSION: Our prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.
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Ciclofosfamida/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Donante no Emparentado , Adolescente , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Área sin Atención Médica , Persona de Mediana Edad , Grupos Minoritarios , Estudios Prospectivos , Sistema de Registros , Adulto JovenRESUMEN
A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens using thymoglobulin for GVHD prophylaxis is limited. We evaluated outcomes of 122 AML patients who received either busulfan (Bu)/fludarabine (Flu)/low-dose total body irradiation (TBI) as RIC (n = 64, 52%) or Bu/Flu as MAC (n = 58, 48%), and thymoglobulin 4.5 mg/kg total dose between day - 3 to - 1 for GVHD prophylaxis. Grades III-IV acute GVHD (aGVHD) was lower with Bu/Flu/TBI compared with Bu/Flu (6.2% vs 26.1%, p = 0.009). At 1 year, Bu/Flu/TBI was associated with similar chronic GVHD (41.2% vs 44.8%, p = 0.75), OS (61.9% vs 56.9%, p = 0.69), relapse rate (29.9% vs 20.7%, p = 0.24), relapse-free survival (52.8% vs 50%, p = 0.80), non-relapse mortality (17.4% vs 29.3%, p = 0.41), and GVHD-free relapse-free survival (24.2% vs 27.5%, p = 0.80) compared with Bu/Flu. Multivariable analysis did not reveal any difference in outcomes between both regimens. In summary, thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with RIC regimen. Both Bu/Flu/TBI and Bu/Flu conditioning regimens yielded similar survival.
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Suero Antilinfocítico/uso terapéutico , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/uso terapéutico , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapéutico , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Anciano , Aloinjertos , Busulfano/efectos adversos , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Infecciones/epidemiología , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Agonistas Mieloablativos/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Linfocitos T , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Donante no Emparentado , Vidarabina/efectos adversos , Vidarabina/uso terapéutico , Irradiación Corporal TotalRESUMEN
The information on the impact of cytokine release syndrome (CRS) on haploidentical donor peripheral blood stem cell transplant (haploPBSCT) outcomes is limited. We retrospectively evaluated 98 patients who underwent haploPBSCT between June 2012 and June 2019 for the onset and severity of CRS per the ASTCT guidelines. The incidence of CRS was 93% (91/98). Outcomes were compared between grade 1-2 and 3-4 CRS. Eighty-one patients developed grade 1-2 CRS (89%) and 10 (11%) developed grade 3-4 CRS. Compared to grade 1-2 CRS, grade 3-4 CRS experienced adverse survival (73.7% vs. 30%, p<.001), inferior relapse-free survival (64.0% vs. 20%, p<.001), and higher non-relapse mortality (NRM) (16.4% vs. 60%, p<.001) at 1-year. Propensity score-based multivariable analyses revealed worse survival (HR 2.71, p=.04), and higher NRM (SHR 4.51, p=.006) with grade 3-4 CRS. Our study shows that grade 3-4 CRS was adversely associated with survival. Therefore, early identification and preventive strategies are warranted.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Ciclofosfamida , Síndrome de Liberación de Citoquinas , Enfermedad Injerto contra Huésped/etiología , Humanos , Recurrencia Local de Neoplasia , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
Limited information is available on the impact of intensity of conditioning regimens in haploidentical peripheral blood stem cell transplant (haploPBSCT) with post-transplant cyclophosphamide (PTcy). We retrospectively compared outcomes of haplo-PBSCT between myeloablative (MAC) (n = 24) and reduced intensity conditioning (RIC) regimens (n = 65). Propensity score-based multivariable analyses were performed to adjust confounding effects of baseline characteristics between both groups. Eighty-nine patients underwent haplo-PBSCT between January 2012 and June 2019. For MAC and RIC, the cumulative incidences of grade III--IV acute GVHD were 4.2% and 3.1%, respectively (p = 0.92), and chronic GVHD were 18.9% and 36.5%, respectively (p = 0.08). Median follow-up for overall survival (OS) after MAC and RIC was 1.86 and 2.2 years, respectively. For MAC and RIC, one-year OS was 68.8% and 67.4%, respectively (p = 0.85); one-year relapse rate was 22.4% and 18.3%, respectively (p = 0.74); one-year relapse-free survival (RFS) was 56% and 59.7%, respectively (p = 0.87); and one-year non-relapse mortality (NRM) was 22% and 21.9%, respectively (p = 0.58). Using propensity score-based multivariable analyses, no difference in OS (HR 0.72, p = 0.51), relapse (SHR 0.63, p = 0.42), RFS (HR 0.74, p = 0.49) and NRM (SHR 1.11, p = 0.87) was noted between RIC and MAC. Our study shows no difference in outcomes between MAC and RIC regimens in haplo-PBSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Humanos , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Acondicionamiento PretrasplanteRESUMEN
The use of G-CSF post allogeneic transplant has become a common practice to accelerate neutrophil engraftment. There is some controversy in its use. To further evaluate the effectiveness, we compared outcomes in patients who underwent PBSCT, either with or without the planned use of G-CSF post SCT. Among consecutive 162 patients from October 2012 to October 2014, 65 patients received G-CSF post-PBSCT, and 97 did not. More patients in G-CSF group received MAC (78% vs. 55%). Patients who received G-CSF had earlier neutrophil engraftment (median days 11 vs. 14) and shorter post-transplant hospital stay (median days 16 vs. 20, p = 0.001). G-CSF use was associated with a higher rate of extensive chronic GVHD (44.3% vs.61.5%, p = 0.027). G-CSF cost the equivalent of 0.25 hospital days but shortened the initial transplant admission by 4 days. Early cost-benefit may be later offset by the economic burden of chronic GVHD and associated complications.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Factor Estimulante de Colonias de Granulocitos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hospitales , Humanos , Incidencia , Tiempo de Internación , Neutrófilos , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Trasplante HomólogoRESUMEN
Anti-thymocyte globulin (ATG) targets in-vivo T lymphocytes. Variations in the recipient absolute lymphocyte count (ALC) might result in a variable exposure of ATG. We hypothesized that recipient ALC on the first day of ATG might predict transplant outcomes. We evaluated 217 patients undergoing 8/8 HLA-matched unrelated donor (MUD) peripheral blood stem cell transplant (PBSCT) between January 2005 and December 2017, and receiving rabbit ATG (Thymoglobulin, total dose 4.5 mg/kg) on days -3, -2 and -1. With a median follow up of 3.68 years for survival (OS), one-year OS, relapse rate, non-relapse mortality (NRM), and relapse-free survival (RFS) were 64.7%, 15.9%, 25.8%, and 58.4%, respectively. Multivariable analysis revealed that ALC > 100 k/mm3 was associated with superior RFS (HR 0.64, p = .03). Our study indicates that ALC on the first day of thymoglobulin affects relapse-free survival in MUD PBSCT when weight-based thymoglobulin is used.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Suero Antilinfocítico , Humanos , Recuento de Linfocitos , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Donante no EmparentadoRESUMEN
Maintenance therapy after first autologous transplant (autoSCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). However, efficacy of maintenance therapy after second autoSCT is unknown. We retrospectively evaluated outcomes of 111 adult MM patients who underwent second autoSCT between January 2000 and December 2018. Lenalidomide up to 15 mg daily or subcutaneous bortezomib 1.3 mg/m2 every 2 weeks was considered maintenance therapy. Outcomes were compared among three groups: no-maintenance (n = 73), lenalidomide (n = 23), and bortezomib maintenance (n = 15). At a median follow-up of 58 months from second autoSCT for survival, 3-year PFS and OS for no-maintenance, lenalidomide, and bortezomib maintenance were 11.2%, 29.9%, and 0%, respectively; and 58.5%, 83.3%, and 67.5% respectively. Lenalidomide maintenance was associated with improved PFS (HR 0.46, p = 0.009) and OS (HR 0.25, p = 0.009) compared to no-maintenance. Lenalidomide maintenance therapy after second autoSCT appears to prolong PFS and OS.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Trasplante de Células Madre , Trasplante AutólogoRESUMEN
Allogeneic stem cell transplant (alloSCT) is considered in diffuse large B cell lymphoma (DLBCL) patients with chemorefractory disease or who have relapsed after autologous SCT. Here we present the first report of alloSCT using the R-BEAM (rituximab, carmustine, etoposide, cytarabine, melphalan) conditioning regimen in DLBCL patients. We retrospectively compared long-term alloSCT outcomes of DLBCL patients who received either R-BEAM (n = 47) or reduced-intensity conditioning (RIC) regimens (n = 23). Seventy patients (median age, 53 years) with DLBCL received alloSCT between January 2005 and December 2017. The median number of pretransplant therapies was 3, and 17 patients (24%) received prior autologous SCT. All received rituximab as a frontline or salvage therapy before alloSCT. The donor was unrelated in 42 patients (60%), and peripheral blood stem cells were commonly used (96%). The 6-month cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) was 36.2% and 8.7% for R-BEAM and RIC, respectively (P = .03). Median follow-up of surviving patients after R-BEAM and RIC was 3.1 and 5.5 years, respectively. Three-year overall survival (OS) after R-BEAM and RIC was 34.4% and 43.4%, respectively (P = .48). At 3 years, R-BEAM was associated with a similar relapse rate (25.5% versus 26.1%, P = .96), nonrelapse mortality (NRM; 39.7% versus 39.1%, P = .98), and relapse-free survival (RFS; 34.8% versus 34.7%, P = .75) compared with RIC. In multivariable analysis lower Karnofsky performance score was associated with lower OS (hazard ratio, .96; P = .05), whereas chemorefractory disease was associated with a higher relapse risk (hazard ratio, 8.8; P = .04). No difference in OS, relapse, NRM, or RFS was noticed between R-BEAM and RIC. R-BEAM regimen seems to be feasible and results in equivalent rates of long-term OS, relapse, NRM, and RFS compared with RIC. However, a significantly higher rate of severe acute GVHD was noticed.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/terapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trasplante de Células Madre , Acondicionamiento PretrasplanteRESUMEN
Impact of Plerixafor (P) mobilized stem cells on immune reconstitution, such as absolute lymphocyte count at day 30 (ALC30), and on long-term outcomes of Multiple Myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) has not been well established. We evaluated total of 469 patients mobilized with G-CSF (G) alone, and 141 patients mobilized with G-CSF plus plerixafor (G+ P). Patients only received plerixafor if they had peripheral blood CD34+ blood count <20/µL on first planned day of collection. Primary endpoint, ALC30, was 1.3 K/µL (range, 0.1-4.5) and 1.2 K/µL (range, 0.1-5.1) for G and G + P, respectively (P =. 61). The median PFS was 2.5 years (95% CI, 2.1-3.2) and 2.8 years (95% CI, 2.0-3.3) for G and G + P, respectively (HR: 1.13; 95% CI, 0.84-1.50; P = .42). The median OS was 6.1 years (95% CI, 4.6-NR) for G group compared to 3.7 years (95% CI, 3.2-NR) for the G + P group (HR: 1.64; 95% CI, 1.12-2.40; P = .01). The median follow-up time for OS was 2.53 years (95% CI, 2.13-2.99) and 1.59 years (95% CI, 1.17-2.02) for G and G+ P group, respectively. In this large retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery or PFS. There was an overall survival difference in patients who were poor mobilizers and could not be mobilized with G-CSF alone.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos/administración & dosificación , Mieloma Múltiple/terapia , Recuperación de la Función , Adulto , Anciano , Autoinjertos , Bencilaminas , Ciclamas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Liver Graft-versus-host disease (GVHD) is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a "non-liver GVHD" group, which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the "non-liver GVHD" group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time-varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.