Patient #1 was an 81-year-old woman with a bulky intra-abdominal mass who was diagnosed with diffuse large B cell lymphoma and failed initial therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone). Obinutuzumab and lenalidomide were planned for salvage therapy as she was unfit for further cytotoxic chemotherapy. The patient did not have splenomegaly or bone marrow involvement. The two drugs were started concomitantly. The platelet count on the first day (day 1) of therapy was 144 × 109/L. Obinutuzumab infusions (100 mg on day 1, 900 mg on day 2) were uneventful; however, the platelets decreased to 33 × 109/L 36 h after the initial infusion. Pseudothrombocytopenia was ruled out, and as a result of a rapid decline of platelet levels and the patient’s concurrent use of antiplatelet drug (aspirin), 1 unit of pooled platelets was transfused. Prothrombin time (PT), partial thromboplastin time (PTT), and D-dimer were within the normal range, whereas fibrinogen was markedly elevated along with other acute-phase reactants. The platelet count remained stable for the next 2 days and recovered to above 90 × 109/L by day 6, and remained so thereafter. The patient demonstrated only partial response to this treatment and succumbed to progressive disease after four courses of therapy without proceeding to a third line of therapy. The severe thrombocytopenia that developed in the first obinutuzumab administration was not observed in the subsequent infusions.

Patient #2 was a 47-year-old man with grade 2 stage 4 follicular lymphoma (FL) and high tumor burden. He had relapsed 16 months after the completion of R-CHOP while undergoing bimonthly rituximab maintenance therapy. Obinutuzumab-ICE (ifosfamide + carboplatin + etoposide) regimen was initiated for salvage therapy and all four drugs were initiated on day 1 when the platelet count was 111 × 109/L due to moderate splenomegaly and bone marrow involvement by lymphoma. The 900 mg obinutuzumab infusion on day 2 was complicated by a grade 3 infusion reaction (fever, chills, rash, and dyspnea); however, the entire dose was eventually administered. The platelet count decreased to 43 × 109/L and 23 × 109/L on days 3 and 4, respectively. PT, PTT, and fibrinogen levels remained normal, and D-dimer was moderately elevated for a few days. One unit of apheresis platelets was transfused on day 4 because of rapidly declining counts and mucosal bleeding. The platelet levels increased following the transfusion and remained over 50 × 109/L till day 11 of therapy when the level decreased again as expected because of the myelosuppressive toxicity of ICE therapy. The patient went on to receive two subsequent courses of O-ICE followed by high-dose chemotherapy with autologous stem cell (ASC) rescue. The patient remains free of progression into his fourth year after the first O-ICE therapy. He received eight further doses of obinutuzumab maintenance after autologous transplantation without the recurrence of acute thrombocytopenia.

Patient #3 was a 41-year-old man with grade 1 FL who suffered from two bulky intra-abdominal masses and moderate kidney failure due to ureteral obstruction. He had failed R-CHOP therapy in the first year and was initiated on O-ICE therapy on an outpatient basis. The infusion of drugs was uneventful. He presented for a check on day 5 of therapy when a rapid decrease of platelet counts from 112 × 109/L on day 1 to 13 × 109/L was noted. PT, PTT, fibrinogen, and D-dimer levels were within the normal range. Platelet counts between days 2 and 4 were unavailable. The patient demonstrated mild bleeding symptoms and coagulation parameters were unremarkable. He was admitted for transfusion support. The platelet levels appropriately increased after each transfusion; however, he remained transfusion dependent till day 23 of therapy probably because of the toxicity of ICE in the following weeks. The patient went on to receive one more O-ICE, high-dose chemotherapy with ASC rescue and obinutuzumab maintenance. Acute thrombocytopenia was not observed on subsequent obinutuzumab courses. However, during the second year of maintenance, he showed disease progression and has recently been started on rituximab lenalidomide therapy.