The Role of Low-dose Anti-thymocyte Globulin as Standard Prophylaxis in Mismatched and Matched Unrelated Hematopoietic Peripheral Stem Cell Transplantation for Hematologic Malignancies

Sakellari, Ioanna; Batsis, Ioannis; Bousiou, Zoi; Mallouri, Despina; Constantinou, Varnavas; Smias, Christos; Yannaki, Evangelia; Kaloyannidis, Panayotis; Παπαϊωάννου, Γεώργιος; Stavroyianni, Niki; Syrigou, Antonia; Sotiropoulos, Damianos; Fylaktou, Asimina; Tsompanakou, Aliki; Saloum, Riad; Anagnostopoulos, Achilles

doi:10.1016/j.clml.2017.06.008

Cited by 24 publications

(19 citation statements)

References 48 publications

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“…Post‐transplant cyclophosphamide (day +3,+4) along with cyclosporine plus MMF (day+5) was the standard GVHD prophylaxis in haploidentical transplants. Unrelated and haploidentical transplant recipients received ATG (5 mg/kg) as part of the conditioning, as previously described . Assessment and grading of aGVHD were performed according to criteria suggested by Glucksberg et al while cGVHD was assessed and graded according to Sullivan et al criteria.…”

Section: Methodsmentioning

confidence: 99%

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Gavriilaki

Batsis

Mallouri

et al. 2018

Clinical Transplantation

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Renewed interest has emerged in transplant-associated thrombotic microangiopathy (TA-TMA) with novel prognostic, diagnostic, and treatment algorithms. We aimed to investigate the incidence, prognostic factors, morbidity, and mortality of TA-TMA in allogeneic hematopoietic cell transplantation (HCT) recipients. We enrolled consecutive HCT recipients (1990-2017). Among 758 patients, 116 (15.5%) were diagnosed with TA-TMA. In the multivariate analysis, TBI-based conditioning, viral infections, acute and chronic GVHD remained independent predictors of TA-TMA. With a median follow-up of 23 (range 0.1-329) months, TA-TMA resulted in significantly lower overall survival (OS). In the multivariate analysis, TA-TMA remained an independent predictor of OS, along with relapse, acute, and chronic GVHD. Among 116 TA-TMA patients, 70 developed renal (56) and/or neurologic (26) dysfunction that would be necessary for TA-TMA diagnosis according to the Bone Marrow Transplant Clinical Trials Network criteria. TA-TMA patients with renal dysfunction showed increased rates of acute GVHD, but no difference in OS compared to patients without renal dysfunction. However, neurologic dysfunction resulted in significantly lower OS. In conclusion, TA-TMA is associated with increased morbidity and mortality in allogeneic transplant recipients. Successful prevention and treatment strategies of infections and GVHD need to be timely employed to improve survival in this complex setting.

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Section: Methodsmentioning

confidence: 99%

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Gavriilaki

Batsis

Mallouri

et al. 2018

Clinical Transplantation

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“…Posttransplant cyclophosphamide (day +3, +4) along with cyclosporine plus MMF (day+5) was the standard GVHD prophylaxis in haploidentical transplants. Unrelated and haploidentical transplant recipients received ATG (5 mg/kg) as part of the conditioning, as previously described …”

Section: Methodsmentioning

confidence: 99%

“…Unrelated and haploidentical transplant recipients received ATG (5 mg/kg) as part of the conditioning, as previously described. 13 Assessment and grading of aGVHD was performed according to criteria suggested by Glucksberg et al, whereas cGVHD was assessed and graded according to the criteria by Sullivan et al 14,15 Site involvement was recorded in both aGVHD and cGVHD patients at diagnosis, pre-and post-ECP evaluation. In particular, for lung GVHD, patients were screened on day +100 with computed tomographic imaging and follow-up spirometry as part of our clinical practice.…”

Section: Study Populationmentioning

confidence: 99%

Favorable impact of extracorporeal photopheresis in acute and chronic graft versus host disease: Prospective single‐center study

Sakellari

Batsis

Mallouri

et al. 2018

J of Clinical Apheresis

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Background Graft vs host disease (GVHD) is the most severe complication of allogeneic hematopoietic cell transplantation. Conventional immunosuppressive therapy increases morbidity and mortality without improving survival. Extracorporeal photopheresis (ECP) has been introduced as an alternative treatment in steroid‐dependent and steroid‐refractory disease. Study design and methods We studied the safety and efficacy of ECP as a second‐ or third‐line treatment in GVHD. Results ECP was administered in 21 patients with grade III‐IV acute GVHD and 88 patients with extensive chronic GVHD, without ECP‐related adverse events. Eight patients receiving four or less ECP sessions were not further analyzed. The majority of acute GVHD patients (84%) presented partial (15) or complete (1) response to ECP. Immunosuppression was reduced in 10 of 19 patients and ceased in 1 of 19 patients. One‐year cumulative incidence (CI) of transplant‐related mortality (TRM) (17.6%) was associated with the lack of response to ECP and steroid refractoriness. With a follow‐up of 17.5 (1.8‐58.3) months, 1‐year overall survival (OS) (52.5%) was independently associated with a higher number of ECP sessions. Regarding chronic GVHD, complete response was achieved in 35 patients, whereas partial response in 25 patients, leading to an overall response rate of 73%. Cutaneous sclerosis manifestations were associated with higher response rates. With a follow‐up of 68.1 (5.4‐283.1) months, 5‐year CI of TRM (24.1%) was associated only with a number of ECP sessions. The 5‐year OS (64.5%) was independently associated with number of ECP sessions and cutaneous manifestations. Conclusion Our findings suggest that ECP is safe and effective for GVHD and should be considered early in the course of GVHD, before irreversible end‐organ damage has been established.

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“…A relatively low-dose ATG is effective in acute GvHD prophylaxis, leading to promising survival rates in matched transplants [24]. Our results indicate that ATG is also effective, but connected to mixed chimerism in very early period after HSCT.…”

Section: Discussionmentioning

confidence: 53%

Impact of Early Chimerism Status on Clinical Outcome in Children with Acute Lymphoblastic Leukaemia after Haematopoietic Stem Cell Transplantation

Lejman

Zaucha‐Prażmo

Zawitkowska

et al. 2019

Preprint

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In this retrospective study we evaluated the clinical impact of very early chimerism after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukaemia (ALL). The study group included 38 boys and 18 girls. Very early chimerism was evaluated on days +7, +14, +21 and +28 after the transplant. Quantitative fluorescence polymerase chain reaction was used to evaluate chimerism. Overall survival (OS) and event-free survival (EFS) were 84% and 80% respectively. OS in group of 24 patients with complete donor chimerism on day +14 was 83% and it did not differ statistically compared to 32 patients with mixed chimerism on day +14 (OS was 84%). The donor type (matched unrelated) and sex (male; p = 0.02 on day +14, p = 0.01 on day +21, p = 0.02 on day 28), number of transplanted cell (above 4,47 x 106 kg; p = 0.036 on day +14) and serotherapy (without ATG; p = 0.05 on day +7, p = 0.016 on day +21, p = 0.023 on day 28) were statistically related to a high level of donor chimerism. Grades II-IV acute graft versus host disease were diagnosed in 23 patients, who presented level donor chimerism above 60% on day 7. The data presented in this study provides valuable insight to the analysis of very early chimerism in children with ALL treated with HSCT.

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The Role of Low-dose Anti-thymocyte Globulin as Standard Prophylaxis in Mismatched and Matched Unrelated Hematopoietic Peripheral Stem Cell Transplantation for Hematologic Malignancies

Cited by 24 publications

References 48 publications

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Favorable impact of extracorporeal photopheresis in acute and chronic graft versus host disease: Prospective single‐center study

Impact of Early Chimerism Status on Clinical Outcome in Children with Acute Lymphoblastic Leukaemia after Haematopoietic Stem Cell Transplantation

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