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The outcomes of patients with acute lymphoblastic leukaemia (ALL) presenting relapse after allogeneic stem cell transplant (allo-SCT) are poor, with few data available in this setting. OBJECTIVE AND METHODS: To evaluate the outcomes of patients with ALL presenting relapsed after allo-SCT, we performed a retrospective study including 132 from 11 centres in Spain. RESULTS: Therapeutic strategies consisted of palliative treatment (n = 22), chemotherapy (n = 82), tyrosine kinase inhibitors (n = 26), immunotherapy with inotuzumab and/or blinatumumab (n = 19), donor lymphocyte infusions (n = 29 pts), second allo-SCT (n = 37) and CAR T therapy (n = 14). The probability of overall survival (OS) at 1 and 5 years after relapse was 44% (95% confidence interval [CI]: 36%; 52%) and 19% (95% CI: 11%; 27%). In the 37 patients undergoing a second allo-SCT, the 5-year estimated OS probability was 40% [22%; 58%]. Younger age, recent allo-SCT, late relapse, 1st complete remission at 1st allo-SCT and chronic graft-versus-host disease confirmed their positive impact on survival in the multivariable analysis. CONCLUSION: Despite the poor prognosis of patients with ALL presenting relapse after a first allo-SCT, some can be satisfactorily rescued and a second allo-SCT still remains a valid option for selected patients. Moreover, emerging therapies really might improve ALL patients outcome when relapsing after an allo-SCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Estudos Retrospectivos , Transplante Homólogo , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco , Prognóstico , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , RecidivaRESUMO
Background: Allogenic stem cell transplant (alloSCT) has been used for several decades as a salvage strategy for relapsed/ refractory Hodgkin lymphoma (R/R HL), being a durable disease control method for some patients. Methods: A unicenter retrospective analysis was performed about alloSCT in R/R HL along 21 years. A survival analysis was made in search for prognostic factors with impact in overall survival (OS)/progression free survival (PFS). Results: Thirty-five patients were reviewed: median age 30years [17-46], 57.1% males, 82.9% had an esclero-nodular HL, 54.3% were in stage II of disease, and 42.9% achieved a complete response before the alloSCT. The donor type was matched-related in 54.3% and the stem cell source was peripheral blood in 97.1% of the grafts. All patients did a reduced intensity conditioning regimen. The overall response rate was 85.7% (complete in 68.6%, partial in 17.1%). Acute graft versus host disease grade II-IVwas seen in 45.7%. Transplant related mortality at day 360 was 17.9%. The median OS was 61 months (95% confidente interval: 33.6-88.3). The median PFS was 1Omonths (95% confidente interval: 3.1-16.9). Patients with >3Oyears at the alloSCT time and a previous autologous SCT showed better OS/PFS in the univariate analysis; having a matched donor and absence of infections along the alloSCT also improved PFS. Conclusions: AlloSCT is a feasible procedure in patients with R/R HL, being able to stabilize the disease in a large number of patients. However, it has a relevant toxicity in patients highly pre-treated.
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BACKGROUND: Acute graft-versus-host disease (GVHD) is a common and life-threatening complication of allogeneic haematopoietic stem cell transplantation (HSCT); there is an urgent unmet need for effective therapies. We aimed to evaluate the Janus kinase 1 inhibitor itacitinib versus placebo, both in combination with corticosteroids, for initial treatment of acute GVHD. METHODS: GRAVITAS-301 was an international, double-blind, adaptive (group sequential design) phase 3 study conducted at 129 hospitals and community practices in 19 countries. Eligible patients were aged 18 years or older, had previously received allogeneic HSCT for a haematological malignancy, developed grades II-IV acute GVHD, and received up to 2 days of systemic corticosteroids. Patients were stratified by clinical standard-risk or high-risk acute GVHD and randomly assigned (1:1), via a centralised interactive voice response system, to receive either oral itacitinib (200 mg) or placebo once daily, both in addition to corticosteroids. The primary endpoint was overall response rate (ORR) at day 28 (defined as the proportion of patients with complete response, very good partial response, or partial response 28 days after the start of treatment). For sample size determination, an absolute improvement in ORR at day 28 over standard therapy of 16% was considered clinically meaningful. Efficacy analyses were performed in the intention-to-treat population; safety analyses included patients who received at least one dose of study drug. GRAVITAS-301 is registered with ClinicalTrials.gov (NCT03139604) and is complete. FINDINGS: Between July 19, 2017, and Oct 3, 2019, 439 patients were randomly assigned to receive either itacitinib plus corticosteroids (n=219; itacitinib group) or placebo plus corticosteroids (n=220; placebo group). 173 (39%) patients were female and 390 (89%) were White. At baseline, 107 (24%) of 439 patients (itacitinib 51 [23%] of 219; placebo 56 [25%] of 220) had clinical high-risk acute GVHD. The ORR at day 28 was 74% (95% CI 67·6-79·7; 162 of 219; complete response 53% [116 of 219]) for itacitinib and 66% (59·7-72·6; 146 of 220; complete response, 40% [89 of 220]) for placebo (odds ratio for ORR 1·45, 95% CI 0·96-2·20; two-sided p=0·078). Grade 3 or worse adverse events occurred in 185 (86%) of 215 itacitinib recipients and 178 (82%) of 216 placebo recipients, and most commonly included thrombocytopenia or platelet count decreased (78 [36%] vs 68 [31%]), neutropenia or neutrophil count decreased (49 [23%] vs 45 [21%]), anaemia (42 [20%] vs 26 [12%]), and hyperglycaemia (26 [12%] vs 28 [13%]). Treatment-related deaths occurred in three of 215 patients (1%) in the itacitinib group and four of 216 (2%) in the placebo group. INTERPRETATION: The observed improvement in ORR at day 28 with the addition of itacitinib versus placebo to corticosteroids did not reach the prespecified significance level. Further studies might provide additional insight into the utility of selective JAK1 inhibition for the treatment of acute GVHD. FUNDING: Incyte.
Assuntos
Doença Enxerto-Hospedeiro , Acetonitrilas/efeitos adversos , Corticosteroides/uso terapêutico , Método Duplo-Cego , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Resultado do TratamentoAssuntos
COVID-19/complicações , Leucemia de Células B/complicações , Leucemia de Células B/mortalidade , Linfoma de Células B/complicações , Linfoma de Células B/mortalidade , Europa (Continente) , Humanos , Imunoterapia Adotiva , Leucemia de Células B/terapia , Linfoma de Células B/terapia , Prognóstico , Resultado do TratamentoRESUMO
Persistent thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Romiplostim and eltrombopag are the currently available thrombopoietin receptor agonists (TPO-RAs), and some studies with very small numbers of cases have reported their potential efficacy in the allo-SCT setting. The present retrospective study evaluated the safety and efficacy of TPO-RAs in 86 patients with persistent thrombocytopenia after allo-HSCT. Sixteen patients (19%) had isolated thrombocytopenia (PT), and 71 (82%) had secondary failure of platelet recovery (SFPR). TPO-RA therapy was started at a median of 127 days (range, 27 to 1177 days) after allo-SCT. The median initial and maximum administered doses were 50 mg/day (range, 25 to 150 mg/day) and 75 mg/day (range, 25 to 150 mg/day), respectively, for eltrombopag and 1 µg/kg (range, 1 to 7 µg/kg) and 5 µg/kg (range, 1 to 10 µg/kg), respectively, for romiplostin. The median platelet count before initiation of TPO-RA therapy was 14,000/µL (range, 1000 to 57,000/µL). Platelet recovery to ≥50,000/µL without transfusion support was achieved in 72% of patients at a median time of 66 days (range, 2 to 247 days). Eighty-one percent of the patients had a decreased number of megakaryocytes before treatment, showing a slower response to therapy (Pâ¯=â¯.011). The median duration of treatment was 62 days (range, 7 to 700 days). Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the patients. At last follow-up, 81% of patients had discontinued TPO-RAs and maintained response, and 71% were alive. To our knowledge, this is the largest series analyzing the use of TPO-RAs after allo-SCT reported to date. Our results support the efficacy and safety in this new setting. Further prospective trials are needed to increase the level of evidence and to identify predictors of response.
Assuntos
Benzoatos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Hidrazinas/administração & dosagem , Pirazóis/administração & dosagem , Receptores Fc/administração & dosagem , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/administração & dosagem , Trombocitopenia , Trombopoetina/administração & dosagem , Adolescente , Adulto , Aloenxertos , Benzoatos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Hidrazinas/efeitos adversos , Lactente , Masculino , Contagem de Plaquetas , Pirazóis/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Espanha , Trombocitopenia/sangue , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Trombopoetina/efeitos adversosRESUMO
Background: Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the PTX3 locus influences the risk of CMV infection is currently unknown. Methods: To dissect the contribution of genetic variation within PTX3 to the development of CMV infection, we analyzed described loss-of-function variants at the PTX3 locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation. Results: We report that the donor, but not recipient, h2/h2 haplotype in PTX3 increased the risk of CMV reactivation after 24 months following transplantation, with a significant effect on survival. Among recipients with h2/h2 donors, CMV seropositive patients as well as those receiving grafts from unrelated donors, regardless of the CMV serostatus, were more prone to develop viral reactivation after transplantation. Most importantly, the h2/h2 haplotype was demonstrated to display an influence toward risk of CMV reactivation comparable to that conferred by the unrelated status of the donor alone. Conclusions: Our findings demonstrate the important contribution of genetic variation in donor PTX3 to the risk of CMV reactivation in patients undergoing HSCT, highlighting a promising prognostic value of donor PTX3 to predict risk of CMV reactivation in this clinical setting.