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Background: Graft failure is an unusual complication of autologous stem cell transplantation (ASCT). It is a life threatening complication where most patients (pts) die because of infections or bleeding. It is defined by absence of neutrophil recovery (>500 ANC) on day +28. It can be primary (there wasn´t a previous neutrophil recovery) or secondary (if there was). Ruling out infections, toxicity of conditioning or poor quality of cells infused, the main cause is still unknown. There is no much literature about GF in ASCT. Treatments proposed are cellular reinfusion or search of a donor for allogeneic stem cell transplantation with poor results. Aims: The aim of this study is to describe our experience in treating such a rare ASCT complication. Primary endpoint is the obtainment of neutrophils (>500) and the platelet engraftment (>20.000) with no transfusion-dependence. Methods: Between 2010 and 2021 a total of 706 pts underwent an ASCT in our institution. 5 pts presented a primary (n=4) or secondary (n=1) GF. We collect the data from these patients. Results: Our incidence of GF is 0.71%, making GF a rare complication of ASCT. 4 pts had a primary GF and 1 had a secondary GF. Peripheral blood was the source in the pts; who were mobilized with G-CSF without any complication. All the pts were infused with more than 2 x106 CD34+ cells /kg (median number of 2.7 (2.2 -3.4)) without any manipulation of the graft. The median viability was 96% (92-99.7). None of the pts had splenomegaly or bone marrow infiltration at the moment of ASCT. These 5 pts had different hematological diseases (3 Multiple Myeloma (MM), 1 composite lymphoma (CL) and 1 primary nervous system lymphoma (PCNSL)). The status of response at ASCT was 3 CR, 1 VGPR (1 MM) and 1 PR (PCNSL). The conditioning regimen used was BUMEL (2 MM), MEL200 (1 MM) BEAM (1 CL) and TT-BCNU (1 PCNSL). All the pts received G-CSF from day +5 after cell infusion. Bone marrow biopsy was made in 3 of these pts, with severe hypoplasia without fibrosis. After diagnosis of GF, in all the pts, the first line treatment was increased dose of G-CSF. 4 pts were also treated with corticoids without any response. 2 pts additionally received previously cryopreserved cells without response. We started empiric treatment with CsA at an initial dose of 1.5mg/kg twice daily in these pts and the median time to reach>500 ANC was 5 days (4-9). Three of these pts could stop CsA treatment after 30 days due to recovery of neutrophil and platelet count. Another one had to be under treatment 150 days. The last one is still on treatment (after 2 months). With a median follow up of 90 months (2-91) all the pts are alive and with a good neutrophil and platelet engraftment. In terms of security, 2 pts developed mild renal failure, managed by dose adjust. No other adverse events were seen in these pts. Summary/Conclusion: CsA is an immunosuppressive drug widely used in aplastic anemia and other bone marrow failure syndromes, due to suppression of haematopoiesis by autoreactive T- lymphocytes. This can also be the pathogenic mechanism of GF. We successfully used empirical CsA treatment in these pts. All the pts but one had an ANC>500 in the first week of treatment with CsA and were able to discontinue the drug soon. Severe infections due to neutropenia are the first causes of death in pts with GF so improvement of ANC decrease is the main goal in the treatment of GF. As CsA is a secure drug, we propose to urgently include this treatment as a curative option in the algorithm of GF management to be taking into account before the allogeneic stem cell trasplantation option.
Cubillas et al. (Wed,) studied this question.