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1.
Lancet ; 401(10392): 1941-1950, 2023 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-37105210

RESUMEN

BACKGROUND: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs. METHODS: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting. FINDINGS: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group. INTERPRETATION: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission. FUNDING: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Estudios Prospectivos , Síndrome de Sézary/terapia , Síndrome de Sézary/etiología , Puntaje de Propensión , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/etiología , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/métodos , Micosis Fungoide/etiología , Micosis Fungoide/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/etiología
2.
Br J Haematol ; 202(2): 284-288, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37183377

RESUMEN

Myeloproliferative neoplasms in blastic phase (MPN-BP) have a dreadful prognosis. We report the characteristics and outcomes of five MPN-BP patients treated with a never-before-described combination of azacytidine and venetoclax (to control BP transformation), added to ruxolitinib (needed to control constitutional symptoms). Median age was 76 years (range 72-84), and worst performance status was 2. The overall response rate was 80%, and the complete remission rate was 40%. With median follow-up of 10.0 months (range 4.2-13.4), median overall survival was 13.4 months (95% CI 4.2-13.4). We did not detect any unexpected treatment-related toxicity, and quality of life was improved.


Asunto(s)
Azacitidina , Trastornos Mieloproliferativos , Humanos , Anciano , Anciano de 80 o más Años , Azacitidina/efectos adversos , Crisis Blástica/tratamiento farmacológico , Resultado del Tratamiento , Calidad de Vida , Trastornos Mieloproliferativos/tratamiento farmacológico
3.
Eur J Haematol ; 110(1): 40-49, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36151965

RESUMEN

BACKGROUND: Haploidentical (haplo-) donors and cord-blood (CB) stem cells provide alternative transplant options in patients lacking an HLA-matched donor. In case of relapse or graft failure after a first alternative allogeneic hematopoietic stem cell transplant (HSCT), a second alternative HSCT (HSCT2) is rarely considered due to a high risk of toxicity. METHODS: A retrospective French multicentre study was performed, including patients with hematologic malignancies who underwent two consecutive HSCT from alternative donors. All data were exported from the national ProMISE database between 2000 and 2016. RESULTS: Forty-three patients (61.4%) received a CB-HSCT2 and 27 (38.6%) a haplo-HSCT2. Indications for HSCT were graft failure (51.4%) or disease progression (48.6%). Two-years probabilities of overall survival, progression-free survival and toxicity-related mortality were 18.5%, 17.8% and 55.8%, respectively. In multivariate analysis, complete remission status at HSCT2 and year of HSCT2 ≥ 2012 were significantly associated with a better outcome (with respectively hazard ratio [HR] = 0.42, p = .002 and HR = 0.5, p = .051). CONCLUSIONS: Neither the indication of HSCT2 nor the source of stem cell was more advantageous towards overall patient survival. A salvage haploidentical or cord-blood stem cell transplantation is a high-risk procedure, that may be considered for patients achieving a complete remission before receiving the second HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios Retrospectivos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Aloinjertos
4.
Acta Oncol ; 61(11): 1332-1338, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36214787

RESUMEN

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting.Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined.Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured.Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B , Adulto , Humanos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Inducción de Remisión , Recurrencia , Linfoma de Células B/terapia , Linfoma de Células B/complicaciones
5.
Cancer ; 126(15): 3438-3447, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32459375

RESUMEN

BACKGROUND: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). In clinical practice, tyrosine kinase inhibitor (TKI) dose reductions can be considered a means of preventing adverse effects and improving quality of life. We hypothesized that administration of low-dose TKIs before treatment discontinuation does not impair TFR in patients with CML who have a deep molecular response (DMR, ≥MR4 ). METHODS: We conducted a retrospective analysis of 77 patients with CML who discontinued treatment with TKIs. Twenty-six patients had been managed with low-dose TKIs before stopping treatment. Patients were to be exposed to TKIs for ≥5 years and to low-dose TKIs for ≥1 year and in DMR for ≥2 years. The loss of major molecular response (MMR) was considered a trigger for restarting therapy. RESULTS: In the low-dose group, 61.5% of patients received second-generation TKIs, and dose reduction was ≥50% for 65.4% of patients. With a median follow-up of 61.5 months, TFR at 12 months was 56.8% in the full-dose TKI group and 80.8% in the low-dose group, and TFR at 60 months was 47.5% and 58.8%, respectively. The median time to molecular recurrence (≥MMR) from TKI discontinuation in the entire cohort was 6.2 months. All patients quickly achieved MMR after resuming TKI therapy. Results appear independent of both dose reduction and potential pretreatment with interferon-α. CONCLUSION: This retrospective study shows that TFR was not impaired by low-dose TKI regimens before TKI cessation in Patients with CML. Nevertheless, prospective randomized clinical trials must be undertaken to analyze the probability of successful TFR in patients managed with TKI dose de-escalation strategies before TKI discontinuation.


Asunto(s)
Relación Dosis-Respuesta a Droga , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inducción de Remisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
6.
Ann Hematol ; 99(8): 1855-1862, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32564196

RESUMEN

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anciano , Aloinjertos , Clofarabina/administración & dosificación , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Estudios Retrospectivos , Tasa de Supervivencia
7.
Biol Blood Marrow Transplant ; 25(12): 2366-2374, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31326611

RESUMEN

Therapy-related myelodysplastic syndrome (t-MDS) after autologous stem cell transplantation (ASCT) is a rare complication with no curative option. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for eligible patients and has been understudied in t-MDS. We report 47 consecutive patients with t-MDS after an ASCT who underwent allo-HSCT with a median age of 58 years (range, 30 to 71 years) at transplantation and a median follow-up of 22 months (range, 0.7 to 107). The median overall survival (OS) was 6.9 months (95% confidence interval [CI], 0 to 19 months). OS rates were 45% (29% to 60%) and 30% (15% to 45%) at 1 and 3 years after transplantation, respectively. On univariate analysis, prior therapy for t-MDS before allo-HSCT (P = .02) and mismatched donors (P = .004) were associated with poor OS. Three-year nonrelapse mortality (NRM) and relapse rates were 44% (25% to 63%) and 41% (22% to 61%), respectively. Mismatched donors (P < .001) were associated with higher NRM and a high-risk MDS (P = .008) with a higher relapse risk. On multivariate analysis, HLA mismatch was associated with higher NRM (hazard ratio, 6.21; 95% CI, 1.63 to 23.62; P = .007). In conclusion, our results suggest that one third of the patients who develop t-MDS after an ASCT for lymphoma are cured after an allo-HSCT. The use of mismatched donors with standard graft-versus-host disease prophylaxis should be avoided in such an indication for allo-HSCT. It will be worthwhile to see if the implementation of cyclophosphamide post-transplantation will improve the outcome with mismatched donors.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma , Síndromes Mielodisplásicos , Neoplasias Primarias Secundarias , Donante no Emparentado , Aloinjertos , Autoinjertos , Supervivencia sin Enfermedad , Linfoma/mortalidad , Linfoma/terapia , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/terapia , Sistema de Registros , Estudios Retrospectivos , Sociedades Médicas , Tasa de Supervivencia
8.
Haematologica ; 104(2): 256-262, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30262561

RESUMEN

Aplastic anemia is a rare but potentially life-threatening disease that may affect older patients. Data regarding the treatment of aplastic anemia in this ageing population remains scarce. We conducted a retrospective nationwide multicenter study in France to examine current treatments for aplastic anemia patients over 60 years old. Our aims were to evaluate efficacy and tolerance, and to analyze predictive factors for response and survival. Over the course of a decade, 88 patients (median age 68.5 years) were identified in 19 centers, with a median follow up of 2.7 years; 21% had very severe and 36% severe aplastic anemia. We analyzed 184 treatment lines, mostly involving the standard combination of anti-thymocyte globulin and cyclosporine-A (33%), which was also the most frequent first-line treatment (50%). After first-line therapy, 32% of patients achieved a complete response, and 15% a partial response. Responses were significantly better in first line and in patients with good performance status, as well as in those that had followed an anti-thymocyte globulin and cyclosporine-A regimen (overall response rate of 70% after first-line treatment). All treatments were well tolerated by patients, including over the age of 70. Three-year survival was 74.7% (median 7.36 years). Age, Charlson comorbidity index and very severe aplastic anemia were independently associated with mortality. Age, per se, is not a limiting factor to aplastic anemia treatment with anti-thymocyte globulin and cyclosporine-A; this regimen should be used as a first-line treatment in elderly patients if they have a good performance status and low comorbidity index score.


Asunto(s)
Anemia Aplásica/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Anemia Aplásica/diagnóstico , Biomarcadores , Médula Ósea/patología , Femenino , Francia/epidemiología , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
9.
Haematologica ; 103(2): 212-220, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29170252

RESUMEN

Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naïve patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×109/L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naïve and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag.


Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Pirazoles/uso terapéutico , Anciano , Suero Antilinfocítico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Terapia Recuperativa/métodos , Encuestas y Cuestionarios , Resultado del Tratamiento
10.
Am J Hematol ; 93(1): 31-39, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28971504

RESUMEN

The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR-ABL1-positive acute myeloid leukemia (AML). Fifty-seven patients (median age, 48 years, range: 19-67) with BCR-ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR-ABL1/ABL < 104 ) at time of SCT in 36.1% (14/40). After SCT, 16 (61.5%) out of 26 patients with MRD positive at transplantation reached MRD negativity. After a median follow-up of 6.3 years (0.7-14.2), NRM, RI, LFS, OS, and GRFS at 5 years were 18.1%, 37%, 44.2%, 53.8%, and 32.1%, respectively. The cumulative incidence of acute GvHD grade II-IV was 16.4%, incidence of chronic GvHD 24.9%, and of extensive cGvHD 21.4%, respectively. In patients who received SCT in CR1, 5-yr NRM, RI, LFS, OS, and GRFS were 15.9%, 36.4%, 46.5%, 59.4%, and 34.9%, respectively. Univariate analysis showed that age (<50 vs. ≥50 years) was associated with RI (5-yr: 22.7 vs. 50%), LFS (5-yr: 61.9 vs. 31.8%), and GRFS (5-yr: 52.4 vs. 18.2%), whereas MRD-negative status before SCT was associated with an improved GRFS (38.9 vs. 16.7%). We conclude that the outcome of patients <50 years of age with BCR-ABL1-positive AML receiving allogeneic SCT in CR is relatively favorable, possibly reflecting the beneficial effect of the use of TKI.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adulto , Anciano , Europa (Continente) , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y Cuestionarios , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo/efectos adversos , Adulto Joven
11.
Am J Hematol ; 93(3): 416-423, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29226497

RESUMEN

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapéutico , Terapia Recuperativa , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Aloinjertos , Antimetabolitos Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Humanos , Inmunosupresores/uso terapéutico , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidad , Transfusión de Linfocitos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/administración & dosificación , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Irradiación Corporal Total , Adulto Joven
12.
Am J Hematol ; 2018 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-29726580

RESUMEN

Matching for HLA-A, -B, -C, and -DRB1 loci (8/8 match) is currently the gold standard for unrelated donor hematopoietic cell transplantation (HCT). In Europe, patients are also matched at the HLA-DQB1 loci (10/10 match). However, there is increasing evidence that matching at HLA-DRB3/4/5 loci may help to lower transplant-related morbidity and mortality. We therefore investigated the impact of HLA-DRB3/4/5 mismatches on outcomes in 1975 patients who received a first 10/10 matched unrelated donor (MUD) HCT in France from 2000 to 2012 for a hematological malignancy. High-resolution typing was performed at HLA-A, -B, -C, -DRB1, -DQB1, -DPB1, and -DRB3/4/5 loci for all donor/recipient pairs. Compared with DRB3/4/5-matched pairs, patients who received a MUD HCT from a DRB3/4/5 mismatched donor had a significantly increased risk of grade II-IV acute graft-versus-host disease (aGVHD) (Adjusted Hazard Ratio (HR) 1.43 (1.07 to 1.90)) associated with lower graft-versus-host disease-free and relapse-free survival (GRFS) (Adjusted HR 1.20 (1.02 to 1.42)). Conversely, we observed no differences in terms of chronic GVHD, nonrelapse mortality, relapse and overall survival. However, we believe that patients stand to benefit from DRB3/4/5 loci being considered for unrelated donor selection to improve GRFS and then quality of life after unrelated HCT.

13.
Blood ; 126(8): 1027-32, 2015 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-26160301

RESUMEN

We analyzed 661 adult patients who underwent single-unit (n = 226) or double-unit (n = 435) unrelated cord blood transplantation (UCBT) following a reduced-intensity conditioning (RIC) consisting of low-dose total body irradiation (TBI), cyclophosphamide, and fludarabine (Cy/Flu/TBI200). Eighty-two patients received rabbit antithymocyte globulin (ATG) as part of the conditioning regimen (ATG group), whereas 579 did not (non-ATG group). Median age at UCBT was 54 years, and diagnoses were acute leukemias (51%), myelodysplastic syndrome/myeloproliferative neoplasm (19%), and lymphoproliferative diseases (30%). Forty-four percent of patients were transplanted with advanced disease. All patients received ≥4 antigens HLA-matched UCBT. Median number of collected total nucleated cells was 4.4 × 10(7)/kg. In the ATG group, on 64 evaluable patients, ATG was discontinued 1 (n = 27), 2 (n = 20), or > 2 days before the graft infusion (n = 17). In multivariate analyses, the use of ATG was associated with decreased incidence of acute graft-versus-host disease (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.17-0.55; P < .0001), higher incidence of nonrelapse mortality (HR, 1.68; 95% CI, 1.16-2.43; P = .0009), and decreased overall survival (HR, 1.69; 95% CI, 1.19-2.415; P = .003). Collectively, our results suggest that the use of ATG could be detrimental, especially if given too close to graft infusion in adults undergoing UCBT following Cy/Flu/TBI200 regimen.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Aloinjertos , Ciclofosfamida/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Estimación de Kaplan-Meier , Trastornos Linfoproliferativos/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Irradiación Corporal Total , Adulto Joven
14.
JAMA ; 318(6): 557-566, 2017 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-28787506

RESUMEN

Importance: Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome. Objective: To evaluate if the early administration of azithromycin can improve airflow decline-free survival after allogeneic HSCT. Design, Setting, and Participants: The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who were at least 16 years old, had undergone allogeneic HSCT for a hematological malignancy, and had available pretransplant pulmonary function test results. Enrollment was from February 2014 to August 2015 with follow-up through April 26, 2017. Interventions: Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen. Main Outcomes and Measures: The primary efficacy end point was airflow decline-free survival at 2 years after randomization. Main secondary end points were overall survival and bronchiolitis obliterans syndrome at 2 years. Results: Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped December 26, 2016. Among 480 randomized participants, 465 (97%) were included in the modified intention-to-treat analysis (mean age, 52 [SD, 14] years; 75 women [35%]). At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). Two-year airflow decline-free survival was 32.8% (95% CI, 25.9%-41.7%) with azithromycin and 41.3% (95% CI, 34.1%-50.1%) with placebo (unadjusted hazard ratio [HR], 1.3; 95% CI, 1.02-1.70; P = .03). Of the 22 patients (5%) who experienced bronchiolitis obliterans syndrome, 15 (6%) were in the azithromycin group and 7 (3%) in the placebo group (P = .08). The azithromycin group had increased mortality, with a 2-year survival of 56.6% (95% CI, 50.2%-63.7%) vs 70.1% (95% CI, 64.2%-76.5%) in the placebo group (unadjusted HR, 1.5; 95% CI, 1.1-2.0; P = .02). In a post hoc analysis, the 2-year cumulative incidence of hematological relapse was 33.5% (95% CI, 27.3%-39.7%) with azithromycin vs 22.3% (95% CI, 16.4%-28.2%) with placebo (unadjusted cause-specific HR, 1.7; 95% CI, 1.2-2.4; P = .002). Conclusions and Relevance: Among patients undergoing allogeneic HSCT for hematological malignancy, early administration of azithromycin resulted in worse airflow decline-free survival than did placebo; these findings are limited by early trial termination. The potential for harm related to relapse requires further investigation. Trial Registration: clinicaltrials.gov Identifier: NCT01959100.


Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Bronquiolitis Obliterante/prevención & control , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Bronquiolitis Obliterante/etiología , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Neoplasias Hematológicas/mortalidad , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Recurrencia , Pruebas de Función Respiratoria , Acondicionamiento Pretrasplante , Trasplante Homólogo , Insuficiencia del Tratamiento
15.
Biol Blood Marrow Transplant ; 22(2): 240-247, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26256942

RESUMEN

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P = .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P = .007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT.


Asunto(s)
Trasplante de Médula Ósea/métodos , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Transfusión de Linfocitos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Donantes de Tejidos , Adulto Joven
16.
Haematologica ; 101(9): 1120-7, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27229716

RESUMEN

Although allogeneic stem cell transplantation is not a standard therapy for multiple myeloma, some patients can benefit from this intense therapy. There are few reports on outcomes after umbilical cord blood transplantation in multiple myeloma, and investigation of this procedure is warranted. We retrospectively analyzed 95 patients, 85 with multiple myeloma and 10 with plasma cell leukemia, receiving single or double umbilical cord blood transplantation from 2001 to 2013. Median follow up was 41 months. The majority of patients received a reduced intensity conditioning. The cumulative incidence of neutrophil engraftment was 97%±3% at 60 days, and that of 100-day acute graft-versus-host disease grade II-IV was 41%±5%. Chronic graft-versus-host disease at two years was 22%±4%. Relapse and non-relapse mortality was 47%±5% and 29%±5% at three years, respectively. Three-year progression-free survival and overall survival were 24%±5% and 40%±5%, respectively. Anti-thymocyte globulin was associated with decreased incidence of acute graft-versus-host disease, higher non-relapse mortality, decreased overall and progression-free survival. Patients with high cytogenetic risk had higher relapse, and worse overall and progression-free survival. In conclusion, umbilical cord blood transplantation is feasible for multiple myeloma patients.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Mieloma Múltiple/terapia , Donante no Emparentado , Adulto , Anciano , Terapia Combinada , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Mieloma Múltiple/mortalidad , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
17.
Am J Respir Crit Care Med ; 191(11): 1242-9, 2015 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-25835160

RESUMEN

RATIONALE: Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects. OBJECTIVES: To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT. METHODS: In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account. MEASUREMENTS AND MAIN RESULTS: At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment. CONCLUSIONS: Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registered with www.clinicaltrials.gov (NCT00624754).


Asunto(s)
Bronquiolitis Obliterante/terapia , Broncodilatadores/uso terapéutico , Budesonida/uso terapéutico , Etanolaminas/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Complicaciones Posoperatorias/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Fumarato de Formoterol , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
18.
Biol Blood Marrow Transplant ; 21(8): 1515-23, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25958294

RESUMEN

Outcomes after umbilical cord blood transplantation (UCBT) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are unknown. We analyzed outcomes of 68 patients with poor-risk CLL/SLL who underwent reduced-intensity (RIC) UCBT from 2004 to 2012. The median age was 57 years and median follow-up 36 months; 17 patients had del 17p/p53mutation, 19 patients had fludarabine-refractory disease, 11 relapsed after autologous stem cell transplantation, 8 had diagnosis of prolymphocytic leukemia, 4 had Richter syndrome, and 8 underwent transplantation with progressive or refractory disease. The most common RIC used was cyclophosphamide, fludarabine, and total body irradiation (TBI) in 82%; 15 patients received antithymocyte globulin. Most of the cord blood grafts were HLA mismatched and 76% received a double UCBT. Median total nucleated cells collected was 4.7 × 10(7)/kg. The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 72% at 60 and 180 days respectively; day 100 graft-versus-host disease (GVHD) (grade II to IV) was 43% and 3-year chronic GVHD was 32%. The CI of relapse, nonrelapse mortality, overall survival, and progression-free survival (PFS) at 3 years were 16%, 39%, 54%, and 45%, respectively. Fludarabine-sensitive disease at transplantation and use of low-dose TBI regimens were associated with acceptable PFS. In conclusion, use of RIC-UCBT seems to be feasible in patients with poor-risk CLL/SLL and improved outcomes were observed in patients with fludarabine-sensitive disease who received low-dose TBI regimens.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Leucemia Linfocítica Crónica de Células B/terapia , Acondicionamiento Pretrasplante/efectos adversos , Adulto , Anciano , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
19.
Biol Blood Marrow Transplant ; 21(3): 489-95, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25529382

RESUMEN

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with higher risk myelodysplastic syndrome (MDS), but the choice of the optimal alternative stem cell source is still a subject of debate in patients lacking an HLA-matched sibling donor. Here, we report on a large series of patients with MDS (N = 631) transplanted either with mobilized peripheral stem cells (PBs) from unrelated donors (n = 502) or with umbilical cord blood transplant (UCB, n = 129) as alternative grafts after reduced-intensity conditioning. Neutrophil engraftment was higher after PB (98% versus 78%, P < .0001). Acute graft-versus-host disease (GVHD) was similar after PB (31%) and UCB (29%), and chronic GVHD incidence was higher after PB (41% versus 23%). Two-year nonrelapse mortality was lower after PB (31% versus 42% P = .03). There was a better overall survival (OS) and disease-free survival (DFS) after PB (49% ± 2% versus 30% ± 4%, P < .0001 and 44% ± 2% versus 28% ± 4%, P < .0001). Multivariate analysis confirmed the advantage of PB for treatment-related mortality, OS, and DFS, whereas relative risk of chronic GVHD was similar. A multivariate analysis comparing PB from a 10/10 HLA-matched donor, PB from a 9/10 HLA-matched donor, and UCB showed an advantage on treatment-related mortality, DFS, and OS only in 10/10 PB. We conclude that in MDS patients lacking an HLA-matched sibling donor, PB from a 10/10 HLA-matched unrelated donor is the preferred source of hematopoietic stem cells. HLA-mismatched unrelated donor or cord blood seem to give similar inferior results except for neutrophil engraftment, which is delayed after UCB.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Síndromes Mielodisplásicos , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante , Donante no Emparentado , Enfermedad Aguda , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Tasa de Supervivencia
20.
Biol Blood Marrow Transplant ; 21(3): 445-53, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25460357

RESUMEN

A prospective phase II multicenter trial was performed with the aim to obtain less than 25% nonrelapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using a reduced-intensity conditioning regimen (RIC) consisting of total body irradiation (2 Gy), cyclophosphamide (50 mg/kg), and fludarabine (200 mg/m(2)). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients who underwent transplantation in first complete remission (CR1) (n = 48) had a higher frequency of unfavorable cytogenetics and secondary AML and required more induction courses of chemotherapy to achieve CR1 compared with the others. The median infused total nucleated cells (TNC) was 3.4 × 10(7)/kg, 60% received double UCBT, 77% were HLA mismatched (4/6), and 40% had major ABO incompatibility. Cumulative incidence of neutrophil recovery at day 60 was 87% and the cumulative incidence of 100-day acute graft-versus-host disease (II to IV) was 50%. At 2 years, the cumulative incidence of NRM and relapse was 20% and 46%, respectively. In multivariate analysis, major ABO incompatibility (P = .001) and TNC (<3.4 × 10(7)/kg; P = .001) were associated with increased NRM, and use of 2 or more induction courses to obtain CR1 was associated with increased relapse incidence (P = .04). Leukemia-free survival (LFS) at 2 years was 35%, and the only factor associated with decreased LFS was secondary AML (P = .04). In conclusion, despite the decreased NRM observed, other RIC regimens with higher myelosuppression should be evaluated to decrease relapse in high-risk AML. (EUDRACT 2006-005901-67).


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Donante no Emparentado , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/administración & dosificación , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Irradiación Corporal Total
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