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Immune reconstitution after human leukocyte antigen (HLA)-mismatched (haploidentical) hematopoietic stem cell transplantation (haplo-HCT) can significantly influence long-term outcomes. The three possible HLA haplotypes after transplantation are: one carried by both the patient and the donor (shared HLA), one by donor only (donor-specific HLA), and one by patient only (host-specific HLA), and the donor T cells remain restricted to one of these three haplotypes. Understanding the presence of donor T cells restricted to each haplotype may provide more detailed insights into post-transplant immune response and potentially provide valuable information for the development of chimeric antigen receptor T cell or T cell receptor T cell constructs. In this study, patients or donors with HLA-A24 or HLA-A2 were tested with HLA-A*24:02- and A*02:01-restricted cytomegalovirus (CMV)-specific tetramers for detecting the respective HLA-restricted T cells. Sixty-four samples from 40 patients were assayed. More than half of the patients at day 90 and all patients by day 900 had shared HLA-restricted T cells. After day 90, half of the patients had donor-specific HLA-restricted T cells, but no host-specific HLA-restricted T cells were found. In the comparative analysis of the transplant types, shared HLA-restricted T cells were positive in all three categories: haplo-HCT (50%), 2-haplo-mis-HCT (75%), and spousal HCT (67%). Furthermore, donor-specific HLA-restricted T cells demonstrated positivity in haplo-HCT at 57% and in 2-haplo-mis-HCT at 60%, with a threshold of 0.01%. Donor-specific HLA-restricted T cells for spousal HCT were not examined due to the lack of an appropriate HLA combination for the tetramers. The presence of shared HLA-restricted T cells explains the host defense after HLA-haploidentical transplantation, while the presence of donor-specific HLA-restricted T cells may account for host defense against hematotropic viruses, such as CMV. However, this study failed to detect host-specific HLA-restricted T cells, leaving the host defense against epitheliotropic viruses unresolved, thus requiring further investigation.
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OBJECTIVE: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy provides a durable response in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The role of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for early evaluation of response in patients with that immunotherapy was evaluated. SUBJECTS AND METHODS: Three separate 18F-FDG PET/CT examinations of 53 patients (29 males, 24 females; median 62 years old) with R/R DLBCL were conducted; before bridging therapy [time of decision (TD)], before CAR-T (tisagenlecleucel, n=37; lisocabtagenemaraleucel, n=16) infusion [time of CAR-T infusion (IT)], and one month (M1) after CAR-T infusion. Response was evaluated based on the Deauville 5-point scale and Lugano criteria. RESULTS: Among 21 patients (39.6%) with complete metabolic response (CMR) at IT-PET, 20 were able to continue CMR, while one showed progression at M1-PET. Among 32 patients (60.4%) with non-CMR at IT-PET, 12, 8, 4, and 8 showed CMR, partial metabolic response (PMR), (non-metabolic response (NMR), and progressive metabolic disease (PMD), respectively, at M1-PET as compared with IT-PET. Evaluations of M1-PET as compared with baseline TD-PET indicated 32, 7, 5, and 9 patients with CMR, PMR, NMR, and PMD, respectively. After a median 10.1 months, 26 patients showed progression and 13 had died from DLBCL. The 32 who achieved CMR showed significantly longer progression-free (P<0.0001) and overall survival (P<0.0001) periods as compared to the 21 non-CMR patients. CONCLUSION: Fluorine-18-FDG PET/CT findings obtained one month after CAR-T cell therapy showed accuracy for early response evaluation and prediction of progression in patients with R/R DLBCL.
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Fluorodesoxiglucosa F18 , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Masculino , Femenino , Persona de Mediana Edad , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/terapia , Resultado del Tratamiento , Anciano , AdultoRESUMEN
Haploidentical hematopoietic cell transplantation (HCT) using glucocorticoids for acute graft-versus-host disease prophylaxis (GC-haplo) may become a curative treatment option for nonremission acute myeloid leukemia (AML). This retrospective study aimed to identify pre-HCT predictors of survival in a cohort of 97 nonremission AML treated with GC-haplo in Hyogo Medical University Hospital between 2010 and 2020. Relapse and primary induction failure included in 70 (72%) and 27 (28%) patients, respectively. Sixty-one patients (63%) had undergone previous HCT. Multivariate analysis revealed that ≤ 6 months' duration between first complete remission (CR1) and first relapse (Rel1) (CR1-Rel1 interval) (hazard ratio 2.11, 95% confidence interval [CI] 1.15-3.89, P = 0.016) and serum albumin before starting the conditioning treatment of ≤ 3.5 g/dL (hazard ratio 1.80, 95%CI 1.09-2.96, P = 0.022) as risk factors for overall survival. Among three groups categorized according to serum albumin and CR1-Rel1 interval, the best 3-year overall survival was observed in patients with albumin > 3.5 g/dL and CR1-Rel1 interval > 6 months or primary induction failure (50.2%, 95%CI 28.9%-68.3%, P < 0.001), revealing that survival could be predicted using albumin and past CR duration in patients with very high-risk AML not in remission before GC-haplo.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Trasplante Haploidéntico/efectos adversos , Estudios Retrospectivos , Inducción de Remisión , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Recurrencia , Albúmina Sérica , Esteroides/uso terapéutico , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND/AIM: Carfilzomib, lenalidomide, and dexamethasone (KRD) therapy is widely used for patients with relapse/refractory multiple myeloma (RRMM). However, the response in patients who underwent assessment for measurable residual disease (MRD) has not been elucidated in a prospective study. We aimed to clarify the response rate and outcome of KRD therapy in patients in RRMM, including those with MRD. PATIENTS AND METHODS: Twenty-one consecutive RRMM patients treated with KRD at 4 Japanese Centers between September 2016 and October 2018 were enrolled and assessed for MRD in the bone marrow (cut-off: 1×10-5) using the EuroFlow-next-generation flow (NGF) method. RESULTS: The median number of therapy lines before KRD was 3 (range=1-6), and the median number of KRD cycles was 4 (range=1-22). As the best overall response post-KRD therapy, 52% (11/21) of patients achieved a MRD negative complete response, 71% (15/21) achieved stringent complete response/complete response, and 14% (3/21) achieved a very good partial response. MRD negativity was achieved in 12 of 16 (75%) and 14 of 21 (67%) patients during and after KRD treatment, respectively. The 2-year progression-free survival and overall survival from the start of KRD therapy were 100% and 100%, respectively, in MRD-positive cases and 88% and 100%, respectively, in MRD-negative cases (median follow-up=1.8 years). Grade 3/4 toxicities were reported in 15 patients (71%), with thrombocytopenia being the most frequent toxicity (6 patients, 29%). CONCLUSION: This is the first study that prospectively assessed MRD of patients with RRMM after KRD therapy. KRD treatment achieved a high MRD negativity rate and good outcomes with manageable toxicities.
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Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiple , Humanos , Dexametasona/efectos adversos , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/etiología , Neoplasia Residual/etiología , Estudios ProspectivosRESUMEN
A 64-year-old man with angioimmunoblastic T-cell lymphoma (AITL) subsequently developed diffuse large B-cell lymphoma (DLBCL) and myelodysplastic syndrome (MDS). Genomic profiling of AITL, DLBCL, and MDS samples revealed that the tumor cells from all samples shared common mutations in TET2 and DNMT3A. In addition, the IDH2 mutation was observed in AITL, and TP53 mutation was observed in DLBCL and MDS. These findings illustrate the clonal relationship between AITL and DLBCL in addition to AITL and MDS, with the latter being increasingly reported. The present findings strongly support the theory of multistep and multilineage tumorigenesis from a common founder clone.
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Although cardiac dysfunction after chimeric antigen receptor (CAR) T-cell therapy has been increasingly reported, the underlying dynamics and pathogenesis are not well documented. Herein, we describe the clinical presentation and treatment for two patients who developed severe acute heart failure after CAR T-cell therapy. Both cases shared several common characteristics, including the bone marrow involvement at the time of CAR T-cell therapy and early onset of cytokine release syndrome (CRS) with fever developing on the day of CAR T-cell infusion. Patients with early onset and/or severe CRS should be carefully monitored for the possibility of heart failure.
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Anti-thymocyte globulin (ATG) is an important prophylactic drug against acute graft-versus-host disease (aGVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study analyzed the pharmacokinetics of rabbit ATG 2.5 mg/kg and its effect against aGVHD in 24 patients undergoing unmanipulated haplo-HSCT. All patients had hematological malignancies not in remission. The median absolute lymphocyte count (ALC) before rabbit ATG administration was 9.5/µL (range 0-41/µL). The grade ≥ II aGVHD group had a significantly lower median rabbit ATG concentration on days 0 (C0) and 7 (C7) and areas under the curve on days 0-7 (AUC0-7) and 0-32 (AUC0-32) than the grade 0-I aGVHD group. Among the four parameters, C0 was the most optimal for predicting aGVHD according to the receiver-operating characteristic (ROC) analysis (area under the ROC curve 0.893; 95% confidence interval 0.738-1.000). The high C0 (≥ 27.8 µg/mL) group had significantly lower cumulative incidence of grade ≥ II aGVHD on day 100 than the low C0 (< 27.8 µg/mL) group (13.8% vs. 88.9%, p < 0.001). In haplo-HSCT, the C0 of rabbit ATG is a good predictor of grade ≥ II aGVHD, even though ALC before rabbit ATG administration is not a predictor of aGVHD.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Suero Antilinfocítico , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
As chimeric antigen receptor (CAR) T cell therapy targeting CD19 has shown favorable outcomes in patients with relapsed or refractory (r/r) mature B cell lymphomas and B cell acute lymphoblastic leukemia (B-ALL), an increasing number of patients are waiting to receive these treatments. Optimized protocols for T cell collection by lymphapheresis for chimeric antigen receptor (CAR) T cell therapy are urgently needed to provide CAR T cell therapy for patients with refractory and progressive disease and/or a low number of lymphocytes owing to prior chemotherapy. The predicted efficiency of CD3+ cell collection in apheresis can guide protocols for apheresis, but a clinically applicable model to produce reliable estimates has not yet been established. In this study, we prospectively analyzed 108 lymphapheresis procedures for tisagenlecleucel therapy at 2 centers. The apheresis procedures included 20 procedures in patients with B cell acute lymphoblastic leukemia and 88 procedures in patients with diffuse large B cell lymphoma, with a median age at apheresis of 58 years (range, 1 to 71 years). After lymphapheresis with a median processing blood volume of 10 L (range, 3 to 16 L), a median of 3.2 × 109 CD3+ cells (range, .1 to 15.0 × 109 cells) were harvested. Collection efficiency 2 (CE2) for CD3+ cells was highly variable (median, 59.3%; range, 11.0% to 199.8%). Multivariate analyses revealed that lower hemoglobin levels, higher circulating CD3+ cell counts, and higher platelet counts before apheresis significantly decreased apheresis CE2. Based on multivariate analyses, we developed a novel formula that estimates CE2 from precollection parameters with high accuracy (r = .56; P < .01), which also suggests the necessary processing blood volume. Our strategy for lymphapheresis should help reduce collection failure, as well as achieve efficient utilization of medical resources in clinical practice, thereby allowing delivery of CAR T cell therapy to more patients in a timely manner.
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Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfocitos TRESUMEN
OBJECTIVES: To determine the impact of the use of hydroxyethyl starch (HES) in granulocyte apheresis using Spectra Optia. BACKGROUND: Granulocyte transfusion (GT) is a therapeutic option for neutropenic patients with severe bacterial or fungal infections. Recent studies in emergency medicine have shown the potential risk of using HES, which is routinely used in granulocyte apheresis to increase yield by sedimenting red blood cells. We hypothesized that the use of a newer device (Spectra Optia) would spare the need for HES. METHODS: We retrospectively compared granulocyte apheresis with HES (HES group, n = 89) and without HES (non-HES group, n = 36) using Spectra Optia. RESULTS: The granulocyte yield was significantly higher in the HES group (7.3 × 1010 vs. 2.0 × 10, p < 0.01) and was attributed to the difference in collection efficiency (36% vs. 7.7%, p < 0.01). The absolute neutrophil count on the following morning of GT was significantly higher in the HES group than in the non-HES group (2460/µl vs. 505/µl, p < 0.01). There were no significant differences in the occurrence of adverse events between the HES and non-HES groups. The renal function was unchanged in both groups after apheresis. CONCLUSIONS: We demonstrated that the advantage of using HES remained unchanged in granulocyte apheresis using Spectra Optia.
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Eliminación de Componentes Sanguíneos , Granulocitos , Humanos , Transfusión de Leucocitos , Estudios Retrospectivos , AlmidónRESUMEN
OBJECTIVES: Achieving a deep response with induction therapy has a major impact on outcomes following autologous stem cell transplantation. Although longer and intensified induction therapy may provide better disease control, longer exposure to lenalidomide negatively affects stem cell yield. We examined the feasibility of 6 cycles of lenalidomide-based triplet induction therapy before stem cell collection in transplant-eligible multiple myeloma patients. METHODS: In this prospective study, patients received a combination of bortezomib, lenalidomide, and dexamethasone for 6 cycles. For patients who did not achieve a deep response after 3 cycles, bortezomib was substituted with carfilzomib for the last 2 cycles (5th and 6th courses). RESULTS: Although only half of the patients achieved a deep response after 3 cycles, all but 1 patient achieved a very good partial response (n = 4) or complete response (n = 5) after completing 6 cycles. Among 9 patients who received cyclophosphamide-based stem cell mobilization, 1 patient required a second mobilization that was successfully performed using plerixafor. After autologous transplantation, 7 patients showed complete response, including 5 with minimal residual disease-negative status. CONCLUSION: This study demonstrates that 6 cycles of lenalidomide-based induction therapy before stem cell collection are a feasible and promising approach for transplant-eligible newly diagnosed multiple myeloma patients.The study is registered at UMIN Clinical Trials Registry as UMIN000026936.Trial registration: UMIN Japan identifier: UMIN000026936.
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Movilización de Célula Madre Hematopoyética , Quimioterapia de Inducción , Lenalidomida/administración & dosificación , Mieloma Múltiple , Adulto , Anciano , Bortezomib/administración & dosificación , Dexametasona , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Estudios ProspectivosRESUMEN
To perform chimeric antigen receptor T (CAR-T) cell therapy in heavily pretreated patients with progressive disease and depleted lymphocytes, an optimized leukapheresis protocol must be established. To probe the effects of patient-related parameters on the collection efficiency of CD3+ cells, we retrospectively analyzed patients with relapsed/refractory diffuse large B-cell lymphoma who underwent leukapheresis for tisagenlecleucel at two centers. A total of 51 patients were analyzed, with a median age at apheresis of 59 years, and precollection hemoglobin levels, CD3+ cell counts, and platelet counts of 9.2 g/dl, 574/µl, and 15.8×104/µl, respectively. A median of 3.0×109 (0.7-8.4) CD3+ cells were harvested with 8.7 (4.0-15.7) l apheresis volume. The collection efficiency 2 (CE2) for CD3+ cells was 61.0% (21.0-127.3). One-day apheresis was sufficient to obtain the designated cell numbers in all cases. Lower hemoglobin levels, higher CD3+ cell counts, and higher platelet counts before apheresis were significantly associated with lower CE2 for CD3+ cells. These results suggest a need to increase the apheresis volume in anemic, lymphocyte- or platelet-rich patients due to an expected low CE2. Erythrocyte transfusions before or during apheresis may be a reasonable option for patients with anemia.
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Leucaféresis , Receptores Quiméricos de Antígenos , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Estudios RetrospectivosRESUMEN
HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II-IV and III-IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Injerto contra Huésped/prevención & control , Haplotipos , Humanos , Estudios Prospectivos , Recurrencia , Acondicionamiento PretrasplanteAsunto(s)
Deleción Cromosómica , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Linfoma Plasmablástico/genética , Linfoma Plasmablástico/terapia , Síndrome de Smith-Magenis , Adulto , Biomarcadores de Tumor , Biopsia , Cromosomas Humanos Par 17 , Femenino , Humanos , Inmunohistoquímica , Mieloma Múltiple/diagnóstico , Linfoma Plasmablástico/diagnóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
Objectives: To examine the prognostic value of interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings after 2-4 cycles of rituximab, plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL) receiving standardized treatment. Results: After a median 3.36 years (range 0.33 to 9.14 years), 24 of the 80 patients had documented relapse. In Interim-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (50.0% vs. 86.4%; p = 0.0012). In End-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (25.0% vs. 84.7%; p < 0.0001). The positive predictive value (PPV) and negative predictive value (NPV) of Interim-PET for predicting relapse or disease progression were 57.1% and 75.8%, respectively, while those for End-PET were 75.0% and 75.0%, respectively. Methods: Eighty DLBCL patients treated with first-line 6-8 R-CHOP courses regardless of interim imaging findings were enrolled. Each underwent FDG-PET/CT scanning at staging, and again during (Interim-PET) and at the end of (End-PET) therapy. PET positivity or negativity at Interim-PET and End-PET as related to progression-free survival (PFS) was examined using Kaplan-Meier analysis. Conclusion: Mid-treatment FDG-PET/CT findings may be useful for determining disease status in patients with DLBCL undergoing induction R-CHOP chemotherapy, though are not recommended for treatment decisions as part of routine clinical practice.
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INTRODUCTION: Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD. METHODS AND ANALYSIS: This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01. ETHICS AND DISSEMINATION: The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000029945.
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Amnios/citología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Mesenquimatosas , Adolescente , Adulto , Anciano , Amnios/trasplante , Femenino , Enfermedad Injerto contra Huésped/terapia , Humanos , Japón , Masculino , Células Madre Mesenquimatosas , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Human leukocyte antigen (HLA) mismatch and the administration of immunosuppressive agents are considered risks for human herpesvirus 6 (HHV-6) reactivation after stem cell transplantation (SCT). However, the incidence of HHV-6 reactivation in HLA-mismatched related SCT remains unknown. METHODS: We monitored plasma HHV-6 DNA loads weekly using real-time quantitative polymerase chain reaction for 5 weeks after SCT and compared serum IL-6 levels in HLA-mismatched SCT groups. RESULTS: Compared with detection in all 11 umbilical cord blood transplantation (CBT) patients (100%), plasma HHV-6 DNA was detected in only 3 of 42 haplo-SCT patients (7.1%) despite the use of methylprednisolone and antithymocyte globulin as graft-vs-host disease prophylaxis and a reduced-intensity conditioning regimen, respectively. Correspondingly, serum IL-6 levels in haplo-SCT patients were significantly lower than those in CBT patients. No HHV-6-associated encephalitis developed in either groups. CONCLUSIONS: Neither HLA disparity nor the use of methylprednisolone and antithymocyte globulin were risk factors for HHV-6 reactivation in our haplo-SCT patients. Rather than increasing risk, the administration of immunosuppressive agents potentially prevented HHV-6 reactivation after haplo-SCT by suppressing IL-6 production.
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Corticoesteroides/uso terapéutico , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/uso terapéutico , Infecciones por Roseolovirus/diagnóstico , Activación Viral/efectos de los fármacos , Adolescente , Adulto , Anciano , Suero Antilinfocítico/uso terapéutico , ADN Viral/sangre , Femenino , Antígenos HLA/genética , Herpesvirus Humano 6/fisiología , Histocompatibilidad , Humanos , Incidencia , Interleucina-6/sangre , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
PURPOSE: To determine the earliest optimal timing for assessment of early response following radioimmunotherapy in non-Hodgkin lymphoma patients using FDG-PET/CT. METHODS: FDG-PET/CT was performed prior to treatment (PET1), at 2 (PET2) weeks, and at 6 (PET3) weeks after 90Y-ibritumomab radioimmunotherapy in 55 patients. Response was evaluated based on the Deauville 5-point scale and Lugano criteria as well as semiquantitative analysis and compared with progression-free survival (PFS). RESULTS: PET 2 showed complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) in 33, 13, 6, and 3 patients, respectively, while PET 3 in 41, 8, 3, and 3 patients, respectively. Mean SUVmax of 168 target lesions decreased over time (PET1, 2, 3; 5.58 ± 2.58, 1.87 ± 1.78, 1.75 ± 2.25, respectively). Progression or recurrence after a median of 12.6 months (range 2.6-72.0 months) was seen in 44 patients. Patients with CMR or metabolic response (CMR + PMR) on PET2 showed significantly longer PFS as compared to those who did not (p = 0.00028 and p = 0.029, respectively). A similar significant difference was observed based on PET3 (p = 0.00013 and p = 0.017, respectively). The same trend was observed when analyzing only the subgroup of patients with follicular lymphoma (N = 43/55) (p < 0.0001). CONCLUSION: Use of FDG-PET/CT findings with Lugano criteria for assessing early response to radioimmunotherapy after 6 weeks allowed for accurate evaluation and prognostic stratification, though scanning after 2 weeks was too soon to precisely evaluate response. KEY POINTS: ⢠The optimal timing of FDG-PET/CT to obtain a suitable tool for assessment of response after 90 Y-ibritumomab radioimmunotherapy of lymphoma has not yet been defined. ⢠Assessment after 6 weeks by FDG-PET/CT using the Lugano criteria accurately evaluates treatment response and prognosis. ⢠FDG-PET/CT performed 2 weeks after radioimmunotherapy is too early as it significantly misses objective responses.
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Anticuerpos Monoclonales/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioinmunoterapia/métodos , Cintigrafía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos B , Progresión de la Enfermedad , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Linfoma de Células B/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios ProspectivosRESUMEN
We report a pilot series of five patients who received stem cell transplantation (SCT) from a spouse for post-transplant relapse or rejection. The inclusion criterion regarding HLA disparities was three or fewer antigen mismatches in the graft-versus-host direction at the HLA-A, B, and DR loci. Four patients received spousal SCT as a third transplant attempt after post-transplant relapse and one as rescue for graft rejection. The reduced intensity conditioning (RIC) regimen consisted of fludarabine, melphalan, and anti-thymocyte globulin (ATG) with 3 Gy of total body irradiation (TBI) for relapse cases and ATG plus 4 Gy of TBI for the rejection case. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. Peripheral blood stem cells were transplanted. Granulocyte engraftment was achieved in all cases between days 9 and 11 (median, 10) with complete spousal chimerism. In three of the five patients, no acute GVHD was observed, while one case developed grade III GVHD and one case grade IV. All four patients evaluable for the anti-leukemic effect achieved complete remission; however, all relapsed between 106 and 334 day post-transplant, and died between days 152 and 548. We suggest that spousal SCT can be performed as a repetitive SCT using a RIC regimen with low-dose ATG and steroid-containing GVHD prophylaxis.