Post Allograft Rituximab Responsive Cytopenia (RRC)
Authors: Kulkarni Samar , Murray John , Kaye David , Dennis Michael , Castleton Anna , Mamat Mohd K , Cavet James , Wiseman Daniel , Somervaille Tim , Sommerfeld Sven , Chasty Richard , Bloor Adrian 
Published: November 2019

Background: Cytopenia post allograft can be multi-factorial. Known causes include viral infection, septicaemia, graft versus host disease (GVHD), nutritional deficiency, myelotoxic drugs, relapsed malignancy but immune mediated cases are increasingly observed. There remains a group of cases where no obvious cause is identified. The incidence of this complication is small but may be underestimated and treatment options and results are not defined.
Aim: This single centre analysis retrospectively evaluated cases of post-transplant cytopenia presumed to be immune mediated or with no obvious cause and response to antiCD20 antibody (Rituximab) therapy. Study period was 2012 to 2019. Data was collected from electronic patient records, case notes and haematology data base.
Results: From 2012 to 2019, 988 patients received allograft (n=390) or autograft (n=598) for haematological malignancy or bone marrow failure syndrome. Twenty-four cases received Rituximab for cytopenia post allograft (24/390, 6.2%). Median age was £9yr. (range: 19-68), 19 were males (79.2%) and allograft were done for severe aplastic anaemia (n=4), Ac. Leukaemia (n=6), Hodgkins disease (n=4), non-Hodgkins lymphoma (n=4), MPD/MDS (n=5) and myeloma (n=1). Conditioning was reduced intensity in n22 case, myeloablative in 2 cases and included campath (n=18) or ATG (n=2) in 20 cases (83.3%). Donor was sibling (n=6) or unrelated (n=22) and 23 (96%) patients received PBSC. All allografts were donor/patient CMV matched (NN: 15, PP: 9). Rituximab was used at a median of 171 days post transplant (range: 55-6174). Cytopenia was trilineage in 8, bilineage in 10 and single lineage in 6 cases. Median haematological parameters were as follows: Hb 78gm/L (68-152), WBC: 2x109/L (0-12), Platelets 28x109/L (4-638). DCT was positive in 7 of the 15 cases where results were available. Seventeen of the 22 cases who had bone marrow evaluation showed hypocellular marrow with no malignancy (3 had normocellular marrow) . Seven of the 10 cases where reticulocyte count pre-rituximab was available, showed response above 2% . Cytopenia was not related to infection, viruses, it B12 or folate deficiency. Response to rituximab therapy was defined as CR (normal counts, transfusion independence, no treatment with steroids or G-CSF), Stable (improvement in counts with platelets>50, Hb>100 and ANC>1.0 without support) or no response. Rituximab was delivered weekly in the dose of 375mg/m2 for 4 weeks.
Twelve patients achieved complete response (50%), 3 achieved stabilization (12.5%) and 9 did not show any response (37%) for overall response rate of 63%. All patients with positive DCT responded to Rituximab (7/7, 100%) but even in negative DCT group 4 responded (4/8, 50%). Response was 100% in single lineage cytopenia (6/6), 40% in bilineage cytopenia (4/10) and 63% in trilineage cytopenia (5/8) [p=0.052]. Three patients received second course of Rituximab for recurrence of cytopenia and all achieved second complete response (all three had autoimmune haemolysis). Numbers are too small to identify the predictors but there was trend towards better outcome in patients younger than 40 yrs. age (10/12 vs. 5/12, p=0.035) and patients with Hodgkins disease (4/4 vs. 11/20, p=0.09) but there was no effect of gender, intensity of conditioning, use of campath/ATG or CMV status. Treatment was well tolerated and infusion reactions were uncommon. We identify that the main drawback of this analysis is substantial amount of missing data, especially haematological investigations that precludes identification of predictors or trends.
Conclusion: Rituximab should be considered as an option for management of post allograft cytopenia with immune aetiology or with no identified cause. Response rate is substantial and the benefit is sustained. It will be useful to have larger cohort of cases to identify the predictors of response.

Disclosures
Kulkarni: Therakos, Clegene: Honoraria. Murray:Therakos: Honoraria. Castleton:Novartis, Pfizer, Amgen: Consultancy, Honoraria. Cavet:AMGEN, Autolus, Celgene, EUSA, Jansen/J&J, Novartis,: Consultancy, Honoraria, Research Funding, Speakers Bureau. Wiseman:Novartis, Celgene: Consultancy, Honoraria. Somervaille:Novartis: Consultancy. Sommerfeld:Gilead: Other: Educational grant. Bloor:Abvie, Gilead, Novartis, Autolus, Celgene, etc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational grant.