Successful autologous bone marrow transplant without the use of blood product ... phoma is poor, and high-dose chemotherapy followed by autologous stem ...
Bone Marrow Transplantation (2000) 26, 227–229 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt
Case report Successful autologous bone marrow transplant without the use of blood product support KK Ballen1, PA Ford2, H Waitkus1, RVB Emmons1, W Levy1, P Doyle1, FM Stewart1, PJ Quesenberry1 and PS Becker1 1
University of Massachusetts Memorial Cancer Center, Worcester, MA; and 2Department of Medicine, Pennsylvania Hospital, Philadelphia, PA, USA
Summary: We describe a successful autologous bone marrow transplant without the use of any blood products. The patient had relapsed large cell lymphoma. He was a Jehovah’s Witness and would not accept transfusions of red blood cells or platelets. He enrolled in our Bloodless Medicine and Surgery Program and was maintained on a regimen of erythropoietin, iron, Amicar, and G-CSF throughout the transplant. He tolerated the transplant well and is alive with no evidence of disease 10 months after autografting. Bone Marrow Transplantation (2000) 26, 227–229. Keywords: lymphoma; Jehovah’s Witness; bloodless
The prognosis for patients with relapsed large cell lymphoma is poor, and high-dose chemotherapy followed by autologous stem cell transplantation is the treatment of choice for young, healthy patients.1 The risks of high-dose chemotherapy include life threatening bleeding from thrombocytopenia and profound anemia.2 Autologous stem cell transplantation is usually associated with the transfusion of 5 to 20 units of red blood cell or platelets, with the potential side-effects of infectious disease transmission, transfusion reactions, and iron overload.3 This report describes a successful autologous stem cell transplant without the use of any blood transfusions in a patient with relapsed lymphoma. Case report A 34-year-old man presented with a mediastinal mass and superior vena cava syndrome in September 1996. He was diagnosed with large cell lymphoma, stage IIB and was treated with cytoxan/adriamycin/vincristine/prednisone (CHOP) followed by mediastinal irradiation. He was well Correspondence: Dr KK Ballen, Division of Hematology/Oncology, U Mass Memorial Health Care, University Campus, 55 Lake Avenue North, Worcester, MA 01655, USA Received 27 October 1999; accepted 16 April 2000
until October 1997 when he was found to have recurrent disease with a large abdominal mass. He was treated with salvage chemotherapy with etoposide/solumedrol/Ara-c/ cisplatin (ESHAP), then relapsed with progressive hematuria secondary to lymphomatous involvement of the kidney and was treated with embolization of the renal artery. He relapsed with pulmonary nodules and was treated with Rituxan (Genentech, San Francisco, CA, USA). The patient’s other medical problems include retinal hemorrhages, obesity, and sleep apnea requiring continuous positive airway pressure (CPAP). The patient is a Jehovah’s Witness and enrolled in the Bloodless Medicine and Surgery Program at University of Massachusetts Memorial Health Care. He is unwilling to accept red blood cells or platelet transfusions because of religious convictions, but accepts erythropoietin, interleukin-11, G-CSF, peripheral blood stem cells, and bone marrow. Informed consent was signed for a bloodless autologous stem cell transplant. Stem cell mobilization was undertaken after the last cycle of ESHAP with G-CSF 10 g/kg/day, interleukin-11 5000 g/day and erythropoietin 15 000 units s.c. each day yielding 1.0 × 106 CD 34+ cells/kg. After a second failed mobilization attempt with G-CSF 10 g/kg/day, he underwent autologous bone marrow harvest of 600 cc in May 1998. This yielded 2.2 × 108 NC/kg. He received iron dextran post-operatively. The harvest was tolerated well, and the transplant was delayed until his hemoglobin exceeded 12. Due to the occlusion of chest vessels secondary to the superior vena cava syndrome, the patient had a femoral Hickman catheter placed which was complicated by laceration of the femoral artery requiring emergency repair and causing moderate blood loss. Transplant chemotherapy was further delayed 4 weeks to achieve a hemoglobin greater than 12. He was admitted for autologous stem cell transplant in December 1998. Hematocrit was 37% and platelet count 83 000 prior to starting chemotherapy. He received a conditioning regimen of cytoxan 1500 mg/m2/day (total dose 6000 mg/m2), etoposide 200 mg/m2 × 8 doses (total dose 1600 mg/m2), and BCNU 300 mg/m2 × 1 dose (total dose 300 mg/m2). Both bone marrow and stem cells to a total dose of 1.41 CD34+ cells/kg were infused. He received
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no platelet or packed red blood cell transfusions throughout. Blood samples were minimized and taken into pediatric tubes. Discarded blood was returned in a closed system. He was maintained on a regimen of G-CSF 5 g/kg/day, erythropoietin 150 units/kg/day s.c., and ferrous sulfate 325 mg p.o. twice a day. When his platelet count dropped below 20 000, he also received Amicar 1–3 g orally every 6 h (Immunex, Seattle, WA, USA). The Amicar was increased to 4 g every 6 h when he experienced epistaxis. The platelet count dropped to 2000 and the hematocrit to 26%. Intravenous iron dextran (950 mg) was again administered. The patient engrafted (neutrophil count greater than 500) on day +12 and was discharged on day +14 following transplant (Figure 1). His post-transplant course has been complicated by radiation pneumonitis, treated successfully with steroids. The patient is currently 10 months post-transplant with no evidence of disease and completely off growth factor support. Cost analysis The product cost of the G-CSF, erythropoietin, iron and Amicar during the transplant admission was US $4,402. The average lymphoma patient in our institution uses a mean of four platelet transfusions and five red blood cell transfusions during inpatient transplant stay for a product cost (not including nursing time) of $10 821. Discussion Patients may be unwilling to accept blood products for religious reasons, or for concerns over transmission of infectious diseases.4 There is variability among Jehovah’s Witnesses and their willingness to accept various biologics
or tissue products. There are several approaches to patients who elect not to accept blood transfusions. Blood loss from frequent blood sampling must be minimized.5 Erythropoietin has been used in the cardiac surgery setting, and there are several approaches to ‘bloodless’ surgery.6 However, a randomized study in patients undergoing autologous stem cell transplant for lymphoma showed that the addition of erythropoietin did not decrease transfusion requirements.7 Interleukin-11 has been used after standard chemotherapy, but has not been successful in decreasing the number of platelet transfusions required after autologous transplant. It was used here only during mobilization, which was suboptimal.8 Aminocaproic acid has been shown to control bleeding in patients with thrombocytopenia, but is rarely used in the post-transplant setting.9 Estrin and colleagues10 have previously described a bloodless autologous stem cell transplant. The present case extends this initial experience with the unique additions of a bone marrow harvest, in a patient with multiple medical problems, who was fortunate to experience quick engraftment, even with the infusion of a relatively low CD34 dose. It is unknown if a large group of subsequent patients would be as fortunate. The current study also includes a cost comparison. While cytokines are expensive, use of cytokines instead of blood products offers a potential cost savings of $6000 per patient. However, if a patient willing to accept blood products was treated with this approach and developed bleeding problems, ensuing transfusions might negate a cost saving. The use of bloodless techniques employed in the surgical setting, may be extended to oncology patients. Our experience shows that autologous stem cell transplantation may be feasible in patients with religious or other objections to blood products. These results suggest that perhaps the
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threshold for transfusion might be raised in selected, younger patients.
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References 7 1 Prince HM, Imrie K, Crump M et al. The role of intensive therapy and autologous blood and marrow transplantation for chemotherapy-sensitive relapsed and primary refractory nonHodgkin’s lymphoma: identification of prognostic groups. Br J Haematol 1996; 92: 880–889. 2 Nevo S, Swan V, Enger C et al. Acute bleeding after bone marrow transplantation – incidence and effect on survival. Blood 1998; 91: 469–477. 3 McKay PJ, Murphy JA, Camerson S et al. Iron overload and liver dysfunction after allogeneic and autologous bone marrow transplantation. Bone Marrow Transplant 1996; 17: 63–66. 4 Ford PA and Henry DH. Using r-HuEPO in patients unwilling to accept blood transfusions. Erythropoiesis 1996; 7: 63–68. 5 Smoller BR, Kruskall MS. Phlebotomy for diagnostic labora-
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tory tests in adults. Pattern of use and effect on transfusion requirements. New Engl J Med 1986; 314: 1233–1235. Rosengart TK, Helm RE, Debois WJ et al. Open heart operations without transfusion using a multimodality blood conservation strategy in 50 Jehovah’s Witness patients: implications for a ‘bloodless’ surgical technique. Am Coll Surg 1997; 184: 618–629. Vannucchi AM, Bosi A, Ieri A et al. Combination therapy with G-CSF and erythropoietin after autologous bone marrow transplantation for lymphoid malignancies: a randomized trial. Bone Marrow Transplant 1996; 17: 527–531. Vredenburgh JJ, Hussein A, Fisher D et al. A randomized trial of recombinant human interleukin-11 following autologous bone marrow transplantation with peripheral blood progenitor cell support in patients with breast cancer. Biol Blood Marrow Transplant 1998; 4: 134–141. Bartholomew JR, Salgia R, Bell WR. Control of bleeding in patients with immune and nonimmune thrombocytopenia with aminocaproic acid. Arch Intern Med 1989; 149: 1959–1961. Estrin JT, Ford PA, Henry DH et al. Erythropoietin permits high-dose chemotherapy with peripheral blood stem-cell transplant for a Jehovah’s Witness. Am J Hematol 1997; 55: 51–52.
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