Hematology-Oncology
Contributions
Type: Publication Only
Background
A major complication of allogeneic stem cell transplantation (allo-SCT) is chronic graft-versus-host disease (cGVHD). Risk factors for the development of cGVHD include prior acute GVHD, increasing patient age, and use of a parous female donor for a male recipient. GVHD is also associated with significant morbidity and mortality, commonly requiring long-term immunosuppressive therapy after allo-SCT. It has been documented that the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells decreases the frequency and severity of cGVHD.
Aims
To describe the frequency and characteristics of cGVHD in 35 patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, at INCMNSZ, from November 1998 to December 2014.
Methods
A retrospective analysis was performed in 35 patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, describing the characteristics and outcome of 12 of them who developed cGVHD, using the Statistical Software Package SPSS v21.0.
Results
Twelve out of 35 patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, from November 1998 to December 2014, developed cGVHD (34.2%). Median age was 33 years (range 16-49), and 60% were male. The patients had a following range of underlying diseases: acute lymphoblastic leukemia (LLA, n=4, 33.3%), myelodysplastic syndrome (n=5, 41.6%), chronic myeloid leukemia (CML, n=2, 16.6%), and acute myeloid leukemia (AML, n=1, 8.3%). Median infused CD34+ stem cell dose was 2.04 x 106/kg. All patients received conditioning with busulphan and cyclophosphamide, and prophylactic immunosuppression with methotrexate (10 mg/m2 days 3, 6, and 11) and cyclosporine A (CsA 5mg/kg) for the first 4 months. The median interval from transplantation to occurrence of cGVHD was 275.3 (range, 101-1359) days. 83.3% of the patients had limited cGVHD (10/12). Among the risk factors associated with cGVHD we identified the following: five male patients were given grafts from female donors, 2 patients with CML developed cGVHD after donor lymphocyte infusion, three patients previously experienced acute GVHD, and only one patient had an antigen mismatch (9/10). In 11 patients (31.4%), hepatic dysfunction was consistent with elevation of transaminases and alkaline phosphatase. Nine patients developed skin involvement characterized by exanthema; 6 had mucous lesions: 2 patients lichen reticularis, 2 developed ulcers, and one leukoplakia. None of the patients had pulmonary or ophthalmic lesions. Initial treatment included steroids in all patients, without complete response and additional Immunosupressive therapy was prescribed including: CsA, sirolimus, mycophenolate mophetyl, cyclophosphamide, ruxolitinib, and imatinib. Median time of duration of immunosuppression therapy was 12.9 months (range, 3-41) with an overall response of 66% (8/12 patients). GVHD associated mortality occurred in one patient, and one patient was lost during follow up. At last follow up, the remaining 10 patients were alive and 8 were out of immunosuppressive therapy without evidence of GVHD.
Summary
Using G-CSF-primed bone marrow as a source of hematopoietic stem cells for allo-SCT is associated with a different pattern of cGVHD tissue impairment, characterized by skin and liver involvement, in most cases mild and limited. At least two immunosuppressive therapy approaches were needed to induce clinical remission. Further studies including a larger number of patients are required in order to validate this strategy.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Bone Marrow, Chronic, Graft-versus-host disease (GVHD)
Session topic: Publication Only
Type: Publication Only
Background
A major complication of allogeneic stem cell transplantation (allo-SCT) is chronic graft-versus-host disease (cGVHD). Risk factors for the development of cGVHD include prior acute GVHD, increasing patient age, and use of a parous female donor for a male recipient. GVHD is also associated with significant morbidity and mortality, commonly requiring long-term immunosuppressive therapy after allo-SCT. It has been documented that the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells decreases the frequency and severity of cGVHD.
Aims
To describe the frequency and characteristics of cGVHD in 35 patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, at INCMNSZ, from November 1998 to December 2014.
Methods
A retrospective analysis was performed in 35 patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, describing the characteristics and outcome of 12 of them who developed cGVHD, using the Statistical Software Package SPSS v21.0.
Results
Twelve out of 35 patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, from November 1998 to December 2014, developed cGVHD (34.2%). Median age was 33 years (range 16-49), and 60% were male. The patients had a following range of underlying diseases: acute lymphoblastic leukemia (LLA, n=4, 33.3%), myelodysplastic syndrome (n=5, 41.6%), chronic myeloid leukemia (CML, n=2, 16.6%), and acute myeloid leukemia (AML, n=1, 8.3%). Median infused CD34+ stem cell dose was 2.04 x 106/kg. All patients received conditioning with busulphan and cyclophosphamide, and prophylactic immunosuppression with methotrexate (10 mg/m2 days 3, 6, and 11) and cyclosporine A (CsA 5mg/kg) for the first 4 months. The median interval from transplantation to occurrence of cGVHD was 275.3 (range, 101-1359) days. 83.3% of the patients had limited cGVHD (10/12). Among the risk factors associated with cGVHD we identified the following: five male patients were given grafts from female donors, 2 patients with CML developed cGVHD after donor lymphocyte infusion, three patients previously experienced acute GVHD, and only one patient had an antigen mismatch (9/10). In 11 patients (31.4%), hepatic dysfunction was consistent with elevation of transaminases and alkaline phosphatase. Nine patients developed skin involvement characterized by exanthema; 6 had mucous lesions: 2 patients lichen reticularis, 2 developed ulcers, and one leukoplakia. None of the patients had pulmonary or ophthalmic lesions. Initial treatment included steroids in all patients, without complete response and additional Immunosupressive therapy was prescribed including: CsA, sirolimus, mycophenolate mophetyl, cyclophosphamide, ruxolitinib, and imatinib. Median time of duration of immunosuppression therapy was 12.9 months (range, 3-41) with an overall response of 66% (8/12 patients). GVHD associated mortality occurred in one patient, and one patient was lost during follow up. At last follow up, the remaining 10 patients were alive and 8 were out of immunosuppressive therapy without evidence of GVHD.
Summary
Using G-CSF-primed bone marrow as a source of hematopoietic stem cells for allo-SCT is associated with a different pattern of cGVHD tissue impairment, characterized by skin and liver involvement, in most cases mild and limited. At least two immunosuppressive therapy approaches were needed to induce clinical remission. Further studies including a larger number of patients are required in order to validate this strategy.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Bone Marrow, Chronic, Graft-versus-host disease (GVHD)
Session topic: Publication Only