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Splenectomy for an adult patient with refractory secondary hemophagocytic lymphohistiocytosis
Biomedicine & Pharmacotherapy 65 (2011) 432–435
Original article
Splenectomy for an adult patient with refractory secondary hemophagocytic lymphohistiocytosis Li-Juan Zhang a,1, Su-Jiang Zhang a,1, Ji Xu a, Jian-Yong Li a, Ling-Ling Wang a, Yi-Xin Hu a, Hong-Xia Qiu a,*,2, Yong-Qian Shu b,* a b
Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China Cancer Center, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 November 2010 Accepted 7 April 2011 Available online 16 June 2011
Treatment regimens of secondary hemophagocytic lymphohistiocytosis (sHLH) are complicated and individualized. CHOP regimen is well known for the treatment of adult sHLH, but it was not so effective for the 56-year-old male patient in our study. Splenomegaly, one of clinical manifestations of HLH, has urged us to investigate the role of splenectomy in HLH patients. Splenectomy is not only beneficial to confirm the underlying diseases, but also beneficial for the treatment of HLH. Here, we present a case diagnosed as sHLH who has recovered from HLH following comprehensive treatment based on splenectomy. The therapeutic value of splenectomy in sHLH needs further study. ß 2011 Elsevier Masson SAS. All rights reserved.
Keywords: Splenectomy Hemophagocytic lymphohistiocytosis Underlying disease
1. Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare disease most commonly characterized by fever, hepatosplenomegaly and cytopenias [1–3]. Secondary HLH (sHLH) is associated with a variety of underlying diseases including infections, malignancies and autoimmune diseases. Infections account for 41% of sHLH cases, but T-cell lymphoma is the leading cause of adult sHLH [4,5]. Treatment regimen of sHLH is variegated. Glucocorticoids and intravenous immunoglobulin (IVIG) were not so effective for the high fever and abnormal laboratory measurements [6]. HLH-2004 immuno-chemotherapy and CHOP regimen have been extensively used, and superior therapeutic effect can be seen among patients with sHLH. Recently, monoclonal antibodies have been used for the treatment of sHLH, including daclizumab [7] and infliximab [8]. However, allogeneic hematopoietic stem cell transplantation (alloHSCT) is the most promising strategy of treatment to cure the disorder of HLH [9]. To our knowledge, splenectomy as an approach to treat sHLH has not been well investigated. Splenomegaly can be commonly found in HLH patients, suggesting that splenectomy can be used as tentative treatment for the disease, especially in refractory sHLH patients. Here, we describe one sHLH case treated with splenectomy. The patient has recovered from
* Corresponding authors. E-mail addresses: [email protected] (H.-X. Qiu), [email protected] (Y.-Q. Shu). 1 These authors contributed equally to this work. 2 Tel: +86-25-83718836-6034; Fax: +86-25-83781120. 0753-3322/$ – see front matter ß 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.biopha.2011.04.008
sHLH following treatment of splenectomy and a series of chemotherapy regimens. 2. Case report 2.1. Before splenectomy A 56-year-old man was admitted into our institution because of intermittent fever up to 39 8C of 9 months’ duration, diffused skin rash, pancytopenia, splenomegaly and hepatitis. The tender and enlarged spleen, 6 cm below the costal margins, was one of the main signs. Serum ferritin (SF 17 600 g/L; normal, 10–250 (g/L), triglyceride (TG 1.75 mmol/L; normal, 0.45–2.25 mmol/L), fibrinogen (FIB 1.7 g/L; normal, 2.0–4.0 g/L), LDH (1066 U/L; normal, 10– 250 U/L) and soluble CD25 level (7429 pg/mL; normal, 0–2000 pg/ mL) were abnormal. Infection surveys indicated negative, including bacterial, fungi, human immunodeficiency virus (HIV), EpsteinBarr virus (EBV), cytomegalovirus (CMV), and so on. 18F-FDG PET/ CT imaging showed multi-organ lesions, including brain parenchyma, lungs, serous cavity, abdominal lymph nodes and spleen (Fig. 1A), and the SUVmax of the spleen was up to 5.7 (Fig. 1B). Bone marrow aspirate smear revealed evidence of hemophagocytosis (Fig. 1C). And cytogenetics analysis of bone marrow showed normal karyotype. Therefore, according to the criteria of HLH-2004 protocol [3], this patient was diagnosed as HLH. Under the suspicion of lymphoma-associated HLH (LAHS) in view of PET/CT imaging, splenectomy was recommended to confirm the diagnosis, but he refused the treatment. Then he underwent two cycles of chemotherapy with CHOP regimen (cyclophosphamide 750 mg/ m2, d1, doxorubicin 50 mg/m2, d1, vincristine 1.4 mg/m2, d1,
L.-J. Zhang et al. / Biomedicine & Pharmacotherapy 65 (2011) 432–435
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Fig. 1. 18F-FDG PET/CT imaging of this patient at initial diagnosis (A, B), and the SUVmax of the spleen was up to 5.7 (B). Obvious hemophagocytosis was found in bone marrow at initial diagnosis (C), which was also found in the spleen post splenectomy (D). No evidence of hemophagocytosis was revealed in bone marrow during continuation therapy of HLH-2004 (E).
prednisone 60 mg/m2, dL-5). Combining therapy including dexamethasone at a dose of 10 mg/d during the chemotherapy intermission, the spleen retracted gradually and cannot be touched at the end of the second CHOP regimen. The blood count and related laboratory markers were improved greatly (Fig. 2). However, the spleen began to swell rapidly one week after two cycles of CHOP, and was found to be 5 cm below the costal margins. Given that the therapeutic effect of previous treatment was not satisfactory, the patient finally accepted splenectomy following two cycles of CHOP regimen.
2.2. After splenectomy Twelve days after the second cycle of CHOP, the patient underwent emergency splenectomy. Although the PLT count was only 48 109/L, the operation was successful. The bulk of the spleen was 20 15.6 8 cm, larger than normal, with a weight of 1370 g. Pathology examination of the spleen tissue indicated no evidence of lymphoma, but hemophagocytosis can be found (Fig. 1D). The flow cytometry (FCM) indicated normal lymphocyte population. Although the underlying disease remained indefinite,
Fig. 2. After treatment with CHOP chemotherapy, as well as dexamethasone during the intermission, the temperature (A) and related laboratory measurements (B, C and D) improved greatly. However, the condition began to deteriorate in a week post the second cycle of CHOP. Chemotherapy drugs were administered at DAY 2 and DAY 16, respectively. The arrows represent the time of chemotherapy.
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L.-J. Zhang et al. / Biomedicine & Pharmacotherapy 65 (2011) 432–435
Fig. 3. Changes of temperature (A) and blood count (B) after splenectomy, with dexamethasone administered at a dose of 3 mg/d. Normal temperature lasted for only 16 days, because the patient was complicated with fungal infection in the courses of Hyper-CVAD (A). The blood count has approximately returned to normal.
the temperature and the blood count began to be improved again (Fig. 3). Meanwhile, another abnormal laboratory examination was also improved, such as soluble CD25 (4050 pg/ml), SF (1010 g/L), and FIB. Subsequently, the patient was received Hyper-CVAD(A) (cyclophosphamide 300 mg/m2, dL-3; vincristine 2 mg, d4,11; doxorubicin 50 mg/m2, d4; dexamethasone 40 mg, dL-4, dL1-14). Given that the previous chemotherapy resulted in severe bone marrow suppression, treatment regimen was adjusted to HLH2004, etoposide at a dose of 200 mg was administered every second week, with the dose of methylprednisolone was gradually reduced to 4 mg/d. After five doses of etoposide, the clinical manifestation and signs of this patient was subsided, and related laboratory markers became normal, such as SF (245 g/L), LDH (210 U/L), and soluble CD25 (1099 pg/ml). No hemophagocytosis was found in the second bone marrow examination (Fig. 1E). He has completely recovered from HLH.
3. Discussion HLH is a fatal disorder characterized by uncontrolled hyperinflammation, eventually results in multiple organ dysfunctions. Early diagnosis by analysis of serum parameters and detection of hemophagocytosis in bone marrow is absolutely mandatory in order to initiate adequate treatment immediately [10]. With regard to the treatment, CHOP regimen is effective for adult sHLH patients, especially in HLH patients associated with lymphoma [11]. Takahashi et al. suggested that HLH without definite etiology should be treated as lymphoma when it is refractory to steroids [12]. The etiology of our patient was indefinite, but he was highly suspected of LAHS based on the PET/CT imaging features (Fig. 1A). Subsequently, chemotherapy with CHOP regimen was administered immediately after hospitalization. A previous study described 17 adult sHLH patients treated with a median of three courses of CHOP regimen, of which 10 patients had response [11]. Five cases of LAHS (5/7) responded to the regimen, and three cases (3/7) acquired complete response (CR). The 2-yr overall survival (OS) rate for 17 patients was up to 43.9%. Although the sHLH patient in our study initially responded to CHOP regimen, therapeutic effect was transient, and he did not acquire CR following two cycles of chemotherapy. Once chemotherapy drugs were withdrawed, the spleen began to swell rapidly. However, the outcome is not determined if the patient continues to receive several cycles of CHOP regimen again. Eradication of the underlying diseases is very important for patients with sHLH. Although the underlying disease of this patient remains unknown, he has acquired 8-month survival after individualized therapy based on splenectomy.
Splenic enlargement is one of the main clinical presentations in HLH patients, which has led to the use of splenectomy for uncontrollable coagulopathy and persistent pancytopenia [13]. As one of treatment choice for HLH, the therapeutic effect of splenectomy has not been extensively reported. Imashuku et al. reported five cases of splenectomized childhood HLH with the findings of haemophagocytes in spleen, of which three died of rapid deterioration after splenectomy [13]. This sHLH patient in our study was improved greatly following the treatment of splenectomy, including the temperature, blood count and other laboratory markers (Fig. 3). Subsequently, chemotherapy was given for this patient once again not only the suspect of diagnosis of lymphoma, but also to control the hyperinflammation of HLH. To date, the patient has been alive for seven months after splenectomy. Splenectomy is also useful for us to confirm the underlying diseases of sHLH. Suzuki et al. described one case of sHLH associated with aggressive natural killer cell leukemia (ANKL), who underwent splenectomy followed 3 years of immunosuppressive therapy [14]. The spleen showed clear evidence of haemophagocytosis, but no obvious malignant foci. Based on the immunochemistry staining and immunophenotype, the underlying disease of ANKL was determined. Han et al. reported one case of sHLH accompanied with spontaneous splenic rupture, which was diagnosed as primary splenic lymphoma after splenectomy [15]. Our study highlights the role of splenectomy for the treatment of sHLH, but the underlying disease of sHLH was not confirmed, with haemophagocytes found in the spleen tissues (Fig. 1D). If this patient received splenectomy before chemotherapy with CHOP regimen, the underlying disease could be certified. Maybe most lymphomatous cells had been killed by the previous chemotherapy drugs, or the secondary factor was not attributed to lymphoma. In conclusion, we describe one case of adult sHLH treated with splenectomy. However, splenectomy for HLH remains controversial [14]. It may be a new approach for refractory sHLH patients, especially among patients with obviously splenomagaly. Combining splenectomy with other therapy is necessary, such as glucocorticoids, IVIG or chemotherapy, because the hyperinflammation is systemic, not limited to the spleen. In addition, the therapeutic benefits of splenectomy must be weighed against the risk of fatal post-splenectomy lymphocytosis [13].
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
L.-J. Zhang et al. / Biomedicine & Pharmacotherapy 65 (2011) 432–435
References [1] Henter JI, Tondini C, Pritchard J. Histiocytic syndromes. Crit Rev Oncol Hematol 2004;50:157–74. [2] Janka GE. Hemophagocytic lymphohistiocytosis. Hematology 2005;10:104–7. [3] Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124–31. [4] Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med 2009;10:387–92. [5] Takahashi N, Chubachi A, Kume M, et al. A clinical analysis of 52 adult patients with hemophagocytic syndrome: the prognostic significance of the underlying diseases. Int J Hematol 2001;74:209–13. [6] Imashuku S. Clinical features and treatment strategies of Epstein-Barr virusassociated hemophagocytic lymphohistiocytosis. Crit Rev Oncol Hematol 2002;44:259–72. [7] Olin RL, Nichols KE, Naghashpour M, et al. Successful use of the anti-CD25 antibody daclizumab in an adult patient with hemophagocytic lymphohistiocytosis. Am J Hematol 2008;83:747–9.
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[8] Henzan T, Nagafuji K, Tsukamoto H, et al. Success with infliximab in treating refractory hemophagocytic lymphohistiocytosis. Am J Hematol 2006;81:59–61. [9] Baker KS, Filipovich AH, Gross TG, et al. Unrelated donor hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 2008;42:175–80. [10] Lackner H, Urban C, Sovinz P, Benesch M, Moser A, Schwinger W. Hemophagocytic lymphohistiocytosis as severe adverse event of antineoplastic treatment in children. Haematologica 2008;93:291–4. [11] Shin HJ, Chung JS, Lee JJ, et al. Treatment outcomes with CHOP chemotherapy in adult patients with hemophagocytic lymphohistiocytosis. J Korean Med Sci 2008;23:439–44. [12] Takahashi N, Chubachi A, Miura I, Nakamura S, Miura AB. Lymphoma-associated hemophagocytic syndrome in Japan. Rinsho Ketsueki 1999;40:542–9. [13] Imashuku S, Obayashi M, Hosoi G, et al. Splenectomy in haemophagocytic lymphohistiocytosis: report of histopathological changes with CD19+ B-cell depletion and therapeutic results. Br J Haematol 2000;108:505–10. [14] Suzuki S, Uozumi K, Utsunomiya A, et al. Aggressive NK cell leukaemia after splenectomy: association with CD95-resistant memory T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome. Eur J Haematol 2008;81:236–41. [15] Han SM, Teng CL, Hwang GY, Chou G, Tsai CA. Primary splenic lymphoma associated with hemophagocytic lymphohistiocytosis complicated with splenic rupture. J Chin Med Assoc 2008;71:210–3.
Original article
Splenectomy for an adult patient with refractory secondary hemophagocytic lymphohistiocytosis Li-Juan Zhang a,1, Su-Jiang Zhang a,1, Ji Xu a, Jian-Yong Li a, Ling-Ling Wang a, Yi-Xin Hu a, Hong-Xia Qiu a,*,2, Yong-Qian Shu b,* a b
Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China Cancer Center, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 November 2010 Accepted 7 April 2011 Available online 16 June 2011
Treatment regimens of secondary hemophagocytic lymphohistiocytosis (sHLH) are complicated and individualized. CHOP regimen is well known for the treatment of adult sHLH, but it was not so effective for the 56-year-old male patient in our study. Splenomegaly, one of clinical manifestations of HLH, has urged us to investigate the role of splenectomy in HLH patients. Splenectomy is not only beneficial to confirm the underlying diseases, but also beneficial for the treatment of HLH. Here, we present a case diagnosed as sHLH who has recovered from HLH following comprehensive treatment based on splenectomy. The therapeutic value of splenectomy in sHLH needs further study. ß 2011 Elsevier Masson SAS. All rights reserved.
Keywords: Splenectomy Hemophagocytic lymphohistiocytosis Underlying disease
1. Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare disease most commonly characterized by fever, hepatosplenomegaly and cytopenias [1–3]. Secondary HLH (sHLH) is associated with a variety of underlying diseases including infections, malignancies and autoimmune diseases. Infections account for 41% of sHLH cases, but T-cell lymphoma is the leading cause of adult sHLH [4,5]. Treatment regimen of sHLH is variegated. Glucocorticoids and intravenous immunoglobulin (IVIG) were not so effective for the high fever and abnormal laboratory measurements [6]. HLH-2004 immuno-chemotherapy and CHOP regimen have been extensively used, and superior therapeutic effect can be seen among patients with sHLH. Recently, monoclonal antibodies have been used for the treatment of sHLH, including daclizumab [7] and infliximab [8]. However, allogeneic hematopoietic stem cell transplantation (alloHSCT) is the most promising strategy of treatment to cure the disorder of HLH [9]. To our knowledge, splenectomy as an approach to treat sHLH has not been well investigated. Splenomegaly can be commonly found in HLH patients, suggesting that splenectomy can be used as tentative treatment for the disease, especially in refractory sHLH patients. Here, we describe one sHLH case treated with splenectomy. The patient has recovered from
* Corresponding authors. E-mail addresses: [email protected] (H.-X. Qiu), [email protected] (Y.-Q. Shu). 1 These authors contributed equally to this work. 2 Tel: +86-25-83718836-6034; Fax: +86-25-83781120. 0753-3322/$ – see front matter ß 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.biopha.2011.04.008
sHLH following treatment of splenectomy and a series of chemotherapy regimens. 2. Case report 2.1. Before splenectomy A 56-year-old man was admitted into our institution because of intermittent fever up to 39 8C of 9 months’ duration, diffused skin rash, pancytopenia, splenomegaly and hepatitis. The tender and enlarged spleen, 6 cm below the costal margins, was one of the main signs. Serum ferritin (SF 17 600 g/L; normal, 10–250 (g/L), triglyceride (TG 1.75 mmol/L; normal, 0.45–2.25 mmol/L), fibrinogen (FIB 1.7 g/L; normal, 2.0–4.0 g/L), LDH (1066 U/L; normal, 10– 250 U/L) and soluble CD25 level (7429 pg/mL; normal, 0–2000 pg/ mL) were abnormal. Infection surveys indicated negative, including bacterial, fungi, human immunodeficiency virus (HIV), EpsteinBarr virus (EBV), cytomegalovirus (CMV), and so on. 18F-FDG PET/ CT imaging showed multi-organ lesions, including brain parenchyma, lungs, serous cavity, abdominal lymph nodes and spleen (Fig. 1A), and the SUVmax of the spleen was up to 5.7 (Fig. 1B). Bone marrow aspirate smear revealed evidence of hemophagocytosis (Fig. 1C). And cytogenetics analysis of bone marrow showed normal karyotype. Therefore, according to the criteria of HLH-2004 protocol [3], this patient was diagnosed as HLH. Under the suspicion of lymphoma-associated HLH (LAHS) in view of PET/CT imaging, splenectomy was recommended to confirm the diagnosis, but he refused the treatment. Then he underwent two cycles of chemotherapy with CHOP regimen (cyclophosphamide 750 mg/ m2, d1, doxorubicin 50 mg/m2, d1, vincristine 1.4 mg/m2, d1,
L.-J. Zhang et al. / Biomedicine & Pharmacotherapy 65 (2011) 432–435
433
Fig. 1. 18F-FDG PET/CT imaging of this patient at initial diagnosis (A, B), and the SUVmax of the spleen was up to 5.7 (B). Obvious hemophagocytosis was found in bone marrow at initial diagnosis (C), which was also found in the spleen post splenectomy (D). No evidence of hemophagocytosis was revealed in bone marrow during continuation therapy of HLH-2004 (E).
prednisone 60 mg/m2, dL-5). Combining therapy including dexamethasone at a dose of 10 mg/d during the chemotherapy intermission, the spleen retracted gradually and cannot be touched at the end of the second CHOP regimen. The blood count and related laboratory markers were improved greatly (Fig. 2). However, the spleen began to swell rapidly one week after two cycles of CHOP, and was found to be 5 cm below the costal margins. Given that the therapeutic effect of previous treatment was not satisfactory, the patient finally accepted splenectomy following two cycles of CHOP regimen.
2.2. After splenectomy Twelve days after the second cycle of CHOP, the patient underwent emergency splenectomy. Although the PLT count was only 48 109/L, the operation was successful. The bulk of the spleen was 20 15.6 8 cm, larger than normal, with a weight of 1370 g. Pathology examination of the spleen tissue indicated no evidence of lymphoma, but hemophagocytosis can be found (Fig. 1D). The flow cytometry (FCM) indicated normal lymphocyte population. Although the underlying disease remained indefinite,
Fig. 2. After treatment with CHOP chemotherapy, as well as dexamethasone during the intermission, the temperature (A) and related laboratory measurements (B, C and D) improved greatly. However, the condition began to deteriorate in a week post the second cycle of CHOP. Chemotherapy drugs were administered at DAY 2 and DAY 16, respectively. The arrows represent the time of chemotherapy.
434
L.-J. Zhang et al. / Biomedicine & Pharmacotherapy 65 (2011) 432–435
Fig. 3. Changes of temperature (A) and blood count (B) after splenectomy, with dexamethasone administered at a dose of 3 mg/d. Normal temperature lasted for only 16 days, because the patient was complicated with fungal infection in the courses of Hyper-CVAD (A). The blood count has approximately returned to normal.
the temperature and the blood count began to be improved again (Fig. 3). Meanwhile, another abnormal laboratory examination was also improved, such as soluble CD25 (4050 pg/ml), SF (1010 g/L), and FIB. Subsequently, the patient was received Hyper-CVAD(A) (cyclophosphamide 300 mg/m2, dL-3; vincristine 2 mg, d4,11; doxorubicin 50 mg/m2, d4; dexamethasone 40 mg, dL-4, dL1-14). Given that the previous chemotherapy resulted in severe bone marrow suppression, treatment regimen was adjusted to HLH2004, etoposide at a dose of 200 mg was administered every second week, with the dose of methylprednisolone was gradually reduced to 4 mg/d. After five doses of etoposide, the clinical manifestation and signs of this patient was subsided, and related laboratory markers became normal, such as SF (245 g/L), LDH (210 U/L), and soluble CD25 (1099 pg/ml). No hemophagocytosis was found in the second bone marrow examination (Fig. 1E). He has completely recovered from HLH.
3. Discussion HLH is a fatal disorder characterized by uncontrolled hyperinflammation, eventually results in multiple organ dysfunctions. Early diagnosis by analysis of serum parameters and detection of hemophagocytosis in bone marrow is absolutely mandatory in order to initiate adequate treatment immediately [10]. With regard to the treatment, CHOP regimen is effective for adult sHLH patients, especially in HLH patients associated with lymphoma [11]. Takahashi et al. suggested that HLH without definite etiology should be treated as lymphoma when it is refractory to steroids [12]. The etiology of our patient was indefinite, but he was highly suspected of LAHS based on the PET/CT imaging features (Fig. 1A). Subsequently, chemotherapy with CHOP regimen was administered immediately after hospitalization. A previous study described 17 adult sHLH patients treated with a median of three courses of CHOP regimen, of which 10 patients had response [11]. Five cases of LAHS (5/7) responded to the regimen, and three cases (3/7) acquired complete response (CR). The 2-yr overall survival (OS) rate for 17 patients was up to 43.9%. Although the sHLH patient in our study initially responded to CHOP regimen, therapeutic effect was transient, and he did not acquire CR following two cycles of chemotherapy. Once chemotherapy drugs were withdrawed, the spleen began to swell rapidly. However, the outcome is not determined if the patient continues to receive several cycles of CHOP regimen again. Eradication of the underlying diseases is very important for patients with sHLH. Although the underlying disease of this patient remains unknown, he has acquired 8-month survival after individualized therapy based on splenectomy.
Splenic enlargement is one of the main clinical presentations in HLH patients, which has led to the use of splenectomy for uncontrollable coagulopathy and persistent pancytopenia [13]. As one of treatment choice for HLH, the therapeutic effect of splenectomy has not been extensively reported. Imashuku et al. reported five cases of splenectomized childhood HLH with the findings of haemophagocytes in spleen, of which three died of rapid deterioration after splenectomy [13]. This sHLH patient in our study was improved greatly following the treatment of splenectomy, including the temperature, blood count and other laboratory markers (Fig. 3). Subsequently, chemotherapy was given for this patient once again not only the suspect of diagnosis of lymphoma, but also to control the hyperinflammation of HLH. To date, the patient has been alive for seven months after splenectomy. Splenectomy is also useful for us to confirm the underlying diseases of sHLH. Suzuki et al. described one case of sHLH associated with aggressive natural killer cell leukemia (ANKL), who underwent splenectomy followed 3 years of immunosuppressive therapy [14]. The spleen showed clear evidence of haemophagocytosis, but no obvious malignant foci. Based on the immunochemistry staining and immunophenotype, the underlying disease of ANKL was determined. Han et al. reported one case of sHLH accompanied with spontaneous splenic rupture, which was diagnosed as primary splenic lymphoma after splenectomy [15]. Our study highlights the role of splenectomy for the treatment of sHLH, but the underlying disease of sHLH was not confirmed, with haemophagocytes found in the spleen tissues (Fig. 1D). If this patient received splenectomy before chemotherapy with CHOP regimen, the underlying disease could be certified. Maybe most lymphomatous cells had been killed by the previous chemotherapy drugs, or the secondary factor was not attributed to lymphoma. In conclusion, we describe one case of adult sHLH treated with splenectomy. However, splenectomy for HLH remains controversial [14]. It may be a new approach for refractory sHLH patients, especially among patients with obviously splenomagaly. Combining splenectomy with other therapy is necessary, such as glucocorticoids, IVIG or chemotherapy, because the hyperinflammation is systemic, not limited to the spleen. In addition, the therapeutic benefits of splenectomy must be weighed against the risk of fatal post-splenectomy lymphocytosis [13].
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
L.-J. Zhang et al. / Biomedicine & Pharmacotherapy 65 (2011) 432–435
References [1] Henter JI, Tondini C, Pritchard J. Histiocytic syndromes. Crit Rev Oncol Hematol 2004;50:157–74. [2] Janka GE. Hemophagocytic lymphohistiocytosis. Hematology 2005;10:104–7. [3] Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124–31. [4] Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med 2009;10:387–92. [5] Takahashi N, Chubachi A, Kume M, et al. A clinical analysis of 52 adult patients with hemophagocytic syndrome: the prognostic significance of the underlying diseases. Int J Hematol 2001;74:209–13. [6] Imashuku S. Clinical features and treatment strategies of Epstein-Barr virusassociated hemophagocytic lymphohistiocytosis. Crit Rev Oncol Hematol 2002;44:259–72. [7] Olin RL, Nichols KE, Naghashpour M, et al. Successful use of the anti-CD25 antibody daclizumab in an adult patient with hemophagocytic lymphohistiocytosis. Am J Hematol 2008;83:747–9.
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[8] Henzan T, Nagafuji K, Tsukamoto H, et al. Success with infliximab in treating refractory hemophagocytic lymphohistiocytosis. Am J Hematol 2006;81:59–61. [9] Baker KS, Filipovich AH, Gross TG, et al. Unrelated donor hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 2008;42:175–80. [10] Lackner H, Urban C, Sovinz P, Benesch M, Moser A, Schwinger W. Hemophagocytic lymphohistiocytosis as severe adverse event of antineoplastic treatment in children. Haematologica 2008;93:291–4. [11] Shin HJ, Chung JS, Lee JJ, et al. Treatment outcomes with CHOP chemotherapy in adult patients with hemophagocytic lymphohistiocytosis. J Korean Med Sci 2008;23:439–44. [12] Takahashi N, Chubachi A, Miura I, Nakamura S, Miura AB. Lymphoma-associated hemophagocytic syndrome in Japan. Rinsho Ketsueki 1999;40:542–9. [13] Imashuku S, Obayashi M, Hosoi G, et al. Splenectomy in haemophagocytic lymphohistiocytosis: report of histopathological changes with CD19+ B-cell depletion and therapeutic results. Br J Haematol 2000;108:505–10. [14] Suzuki S, Uozumi K, Utsunomiya A, et al. Aggressive NK cell leukaemia after splenectomy: association with CD95-resistant memory T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome. Eur J Haematol 2008;81:236–41. [15] Han SM, Teng CL, Hwang GY, Chou G, Tsai CA. Primary splenic lymphoma associated with hemophagocytic lymphohistiocytosis complicated with splenic rupture. J Chin Med Assoc 2008;71:210–3.