Abstract

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A 39-year old female Jehovah’s Witness patient presented with a relapse of B-cell follicular non-Hodgkin’s lymphoma.We had to avoid administration of any blood components as part of the treatment due to the conflict with the patient’s religious beliefs. Instead of administering a high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation we identified radioimmunotherapy with ibritumomab tiuxetan as the best therapeutic option in the circumstances. The treatment with ibritumomab tiuxetan led to severe and long-term inhibition of bone marrow with prolonged pancytopenia, extreme low count of hemoglobin level, platelets and neutrophils. During the entire post-treatment period the patient has refused to receive red blood cells, plasma or platelet transfusions. The patient has spent 11 months in cytopenia without life-threatening bleeding or organ failure and until now the patient is surviving in a complete remission with normal blood cell counts.

Introduction

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Ibritumomab tiuxetan is a monoclonal antibody anti-CD20 labeled with yttrium radionuclide ⁹⁰Y. It represents an effective radioimmunotherapy for patients with relapsed B-cell non-Hodgkin’s lymphoma [1,2]. The main adverse effect of ibritumomab tiuxetan is temporary myelosupression. In a group of 349 patients who were given a dose of 14,8 Mbq/kg (0,4 mCi/kg), 28% developed hematologic toxicity grade 3 with neutropenia (0,5-1,0x10⁹/l), 52% with thrombocytopenia (10-50x10⁹/l) and 14% with anemia (65-80g/l) [3,4]. Grade 4 toxicity was seen in 30% with neutropenia (9/l), 10% with thrombocytopenia (9/l) and 3% with anemia (

Case Report(s)

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The 39-year old woman, Jehovah’s Witness had been diagnosed in May 2002 with a B-cell Non-Hodgkin’s follicular lymphoma, grade 2, CD20-positive, initial stage IV.A, with bone marrow infiltration of 10%, cervical, mediastinal, retroperitoneal lymphadenopathy and splenomegaly. In compliance with her religious beliefs the patient refused any treatment which would require blood transfusions or replacement of other human blood components. During the period from July 2002 to September 2003 she recieved combined chemotherapy CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with the anti-CD20 monoclonal antibody rituximab as first line treatment. Due to lack of effectiveness and persistent abdominal lymphadenopathy, and in order to avoid the administration of transfusion support, the patient was excluded from high-dose chemotherapy treatment followed by autologous peripheral blood stem cells transplantation. From September 2003 to October 2004 she underwent treatment with interferon alpha (at the time rituximab was not available for maintenance therapy). During the interferon treatment the marrow infiltration progressed up to 15%. Till January 2005 lymphadenopathy and splenomegaly increased. As the second-line treatment, from April 2005 to September 2005, she underwent, without blood transfusions, oral treatment FluCy (fludarabine, cyclophosphamide) and rituximab resulting in complete remission and persistent minimal residual disease in bone marrow under 5%. By June 2007 lymphadenopathy in the mesenterium, retroperitoneum, hepatosplenomegaly and new deposites in the spleen emerged. However, there was no finding of bone marrow infiltration. After a consultation with the patient we chose a salvage treatment option with DHAP (cDDP, Ara-C, DXM) at 50% reduced doses because of hematologic toxicity, followed by radioimmunotherapy with ibritumomab tiuxetan (90Y-anti-CD20) after the reduction of lymphadenopathy [1]. In the period from August 2007 to September 2007, after 2 cycles of DHAP, CT scan revealed regression of the lymphadenopathy to 25mm and extinction of the splenic deposits described previously. Shortly before administration of ibritumomab tiuxetan a PET exam in November 2007 confirmed remission of the disease, without any area of pathological increased metabolisation of 18FDG on both sides of diaphragm. On 30th of November 2007 ibritumomab tiuxetan was administered at a dose of 31,01 mCi (0,4 mCi/kg).
On the 32nd day after ibritumomab tiuxetan at a total dose of 1147,3 Mbq (31,01 mCi) the patient developed severe pancytopenia without any symptoms of infection or bleeding. On the same day leukocytes decreased to 0,83x109/l, platelets to 10x109/l and mild anemia to 92g/l. Grade 4 neutropenia remained up to 67th day, thrombocytopenia to 81st and hemaglobin to 178th day after the administration of ibritumomab tiuxetan, grade 3 neutropenia to 92nd day, thrombocytopenia to 104th day and anemia to 252nd day. Extremely low level of hemoglobin was found on day 78 (17g/l). The patient survived more than 38-day period with hemoglobin level below 30g/l [Illustration 1,2.]. At the time of severe myelosuppression one episode of febrile neutropenia occurred and was successfully treated with empiric antibiotic therapy (PIP/TAZO). No severe or life-threatening bleeding occurred, but some petechias appeared on the skin. The effect of severe anemia resulted in on physical inactivity of the patient. There was no organ failure or cardiac chest pain. Medication during hospitalization included haemostatic agents (etamsylat, pamba, vitamin K), gastrointestinal tract prophylaxis (proton-pump inhibitor, stool softener), cardiac vasodilatants (isosorbit mononitrate), substrates for haemopoesis (folate, vitamin B6, iron supplementation), haematopoietic growth factors (pegfilgrastim, epoetin beta) and oxygen support. In case of life-threatening bleeding terlipresin and recombinant activated factor VII (rFVIIa) were prepared [7,8,9]. Rapid production of reticulocytes occurred from day 60. Sternal aspirate of bone marrow on 81st day established signs of regeneration of white and red blood cell lines. The patient was repeatedly instructed about risk of her decision. She was conscious with preserved intellectual skill and rational thinking, but consistently refused transfusion of erythrocytes, plateletes, fresh frozen plasma, or its derivatives, including human albumin. She preferred her own death rather than agreeing to substitution of blood components. She agreed with the application of haematopoietic growth factors (pegfilgrastim, epoetin beta) and recombinant clotting factor rVIIa [7,8,9]. During the severe myelosuppression period patient was hospitalizated for 69 days from January 4th 2008 to March 12th 2008. Recovery of the haemopoesis was maintained until November 11th 2008 (WBC 3,76x109/l, NEU 1,84x109/l, Hb 105g/l, PLT 97x109/l) [Illustration 1,2.]. CT examination confirmed the complete remission of the disease, and the last blood count showed recovery of the functional bone marrow.

Conclusion

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This case of a Jehovah’s Witness, suffering from relapsed B-cell non-Hodgkin’s lymphoma and unexpected long-term decline of hematological parameters after treatment with ibritumomab tiuxetan, is an interesting example of solving possible life-threatening complications. when an patient refuses blood products. This patient is now living in a complete remission after several months of life-treating myelosuppression without any blood cell supplementation.

Authors contribution(s)

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The author declares that he has no competing interests.

References

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1. Witzig TE, Flinn IW, Gordon LI, Emmanouilides E, Czuczman MS, Saleh MN, Cripe l, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol 2002, 20:3262-3269.
2.Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-Lopez AJ, Multani PS, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol 2002, 20:2453-2463.
3.Wiseman GA, Gordon LI, Multani PS, Witzig TE, Spies S, Bartlett NL, Schilder RJ, Murray JL, Saleh M, Allen RS, Grillo-Lopez AJ, White CA. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin’s lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood 2002, 99:4336-4342.
4.Gordon LI, Witzig TE, Molina A, Czuczman M, Emmanouilides C, Joyce R, Vo K, Theuer C, Pohlman C, Bartlrtt N, Wiseman G, Darif M, White C. Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with previously treated B-cell lymphoma. Clin Lymphoma 2004, 5:98-101.
5.Witzig TE, White CA, Gordon LI, Emmanouilides CM, Murray Jl, Lister J, Multani PS. Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade follicular, or transformed non-Hodgkin’s lymphoma. J Clin Oncol 2003, 21:1263-1270.
6.Witzig TE, White CA, Gordon LI. Zevalin® radioimmunotherapy can be safely administered to patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL). Blood 2001, 97:606a, (Abstract 2539).
7.Brown NM, Matthews B, Ford PA. Treatment of a Jehovah’s Witness using a transfusion-free autologous stem cell transplant protocol. Commun Oncol 2006, 3:776-781.
8.Virchis A, Hughes C, Berney S. Severe gastrointestinal haemorrhage responding to recombinant factor VIIa in a Jehovah’s Witness with refractory immune thrombocytopenia. Hematol J 2004, 5:281-282.
9.Barnes C, Blanchette V, Canning P, Carcao M. Recombinant fVIIa in the management of intracerebral haemorrhage in severe thrombocytopenia unresponsive to platelet-enhancing treatment. Transfus Med 2005, 15:145-150.

Source(s) of Funding

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none

Competing Interests

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none

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