© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273
Case report
Cryptococcal meningitis post autologous stem cell transplantation S. Chaaban, L.J. Wheat, M. Assi. Cryptococcal meningitis post autologous stem cell transplantation. Transpl Infect Dis 2014. All rights reserved Abstract: Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with nonHodgkin’s lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/lL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSF Cryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.
Cryptococcus neoformans is an encapsulated fungus known to cause a wide array of diseases ranging from colonization of the lungs to a more serious and deadly illness when it affects the central nervous system (CNS). It has been considered the most common cause of fungal-associated meningitis in both immunocompetent and immunocompromised individuals (1). Immunocompromised hosts include those with human immunodeficiency virus (HIV) infection, prolonged
S. Chaaban1, L.J. Wheat2, M. Assi3 1
Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, Kansas, USA, 2 MiraVista Diagnostics, Indianapolis, Indiana, USA, 3 Infectious Disease, Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, Kansas, USA
Key words: Cryptococcus; meningitis; autologous stem cell transplant; non-Hodgkins lymphoma Correspondence to: Maha Assi, MD, MPH, Infectious Disease, Department of Internal Medicine, University of Kansas School of Medicine-Wichita, 1010 North Kansas, Wichita, KS 67214, USA Tel: (316) 293-2650 Fax: (316) 293-1878 E-mail: [email protected]
Received 8 April 2013, revised 2 September 2013, 7 December 2013, accepted for publication 18 December 2013 DOI: 10.1111/tid.12216 Transpl Infect Dis 2014: 0: 1–4
treatment with glucocorticoids, organ transplantation, and malignancy (2). Prognosis is affected by the time interval between onset of symptoms to diagnosis and treatment (3). Fluconazole has been effective in treatment. Resistance has rarely been reported in an immunocompetent patient, but has been described in HIV-infected individuals (4). We present the case of a 41-year-old patient with peripheral T-cell non-Hodgkin’s lymphoma who developed Cryptococcus meningitis
1
Chaaban et al: Cryptococcal meningitis post autologous SCT
after autologous stem cell transplant (SCT) and while receiving fluconazole as prophylaxis.
Case presentation We present a 41-year-old man, known to be HIV negative, with peripheral T-cell non-Hodgkin’s lymphoma stage 4 B. He was initially treated with 3 cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) chemotherapy and then underwent autologous peripheral blood SCT with BEAC (BiCNU, etoposide, ARA-C, and cyclophosphamide) as the conditioning regimen. Transplant prophylaxis started on day 2 and consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, the patient developed headache with associated fever and change in mental status. His peripheral white blood cell count (WBC) then was 700/lL (4800–10,800/lL). Magnetic resonance imaging with contrast revealed both dural and cortical enhancement suggestive of meningoencephalitis. A lumbar puncture was performed and cerebrospinal fluid (CSF) analysis revealed a WBC of 39/mm3 (normal 0–10/mm3) with 77% lymphocytes, protein 63 mg/dL (normal 15–45 mg/dL), glucose 38 mg/dL (normal 40–70 mg/dL), CSF pressure 20.5 cmH2O (normal 9–18 cmH2O), and a positive cryptococcal antigen (Table 1). CSF culture confirmed Cryptococcus neoformans. The patient worked as an educator at a small community college, had no farming activity, and no other environmental exposures. The patient was treated with liposomal amphotericin B (L-AmB) 5 mg/kg intravenously daily and flucytosine 37.5 mg/kg per DobHoff tube every 6 h. Serial lumbar punctures were performed to decrease intracranial pressure and to follow CSF analysis (Table 1). The patient gradually became more awake and oriented, but did not recover his full mental abilities.
He was switched to fluconazole 400 mg daily after 3 weeks of AmB therapy, with sterilization of the CSF, and a negative CSF Cryptococcus antigen and culture. He was transferred to long-term care for nursing care and physical rehabilitation.
Discussion C. neoformans is a ubiquitous saprophyte that has been isolated from pigeon droppings, from heartwood of several tree species in South America and India, and from homes of HIV-infected African patients (5). This small encapsulated yeast usually enters the body via inhalation. Cryptococcus causes a mild pulmonary infection that, depending on the host immune system and the amount and virulence of the organism, could either be cleared, cause a latent infection, or disseminate (2, 5, 6). C. neoformans has the tendency to infect the CNS, thus leading to meningitis and meningoencephalitis (2). Cryptococcal infections constitute 2% of CNS infections in patients with an underlying hematological malignancy (7). Cryptococcus usually affects male patients more than female, in their third and fourth decades of life (8). Dissemination usually occurs in patients who have a defective T-cell immune system, mainly in patients with malignancy, on immunosuppressive medications, and in those who suffer from autoimmune disease, HIV infection, or sarcoidosis (5). It has been shown in Australia and the United States that 40.5–70.3% of patients have an underlying disease (8). Cryptococcus is considered to be the main cause of death secondary to mycosis in HIV-infected patients, thus stressing the role of cell-mediated immunity in eradication of the disease (6). Cryptococcus after hematopoietic SCT (HSCT) is a rare disease when compared with solid organ transplant (SOT). The proposed mechanism is that transplant-related antineoplastic agents lead to complete
Cerebrospinal fluid (CSF) test results Tests
Day 0
Day 1
Day 3
Day 12
Day 19
Day 41
CSF protein
63
65
49
31
CSF glucose
38
34
50
60
Negative
Negative
Negative
Negative
CSF cryptococcal antigen
1:64
1:64
Opening pressure (in H2O)
20.5 cm
21 cm
CSF fungal culture
Positive
Positive
1:128
Positive
Table 1
2
Day 5
Transplant Infectious Disease 2014: 0: 1–4
1:4 35 cm
20 cm
Negative
Negative
Chaaban et al: Cryptococcal meningitis post autologous SCT
List of similar cases of cryptococcal meningitis after stem cell transplantation in the literature1
Author (ref.)
Transplant source
Age/gender
Underlying condition
Onset
Conditioning regimen
Treatment
Outcome
Mineiro et al. (12)
Allogeneic
12/F
ALL
64 days
Total body irradiation, thiotepa, and cyclophosphamide
AmB and 5-FC
Death
Mendpara et al. (10)
Autologous
42/F
MM
4 months
Melphalan and cyclophosphamide
L-AmB, 5-FC, and Flu
Alive
Rimek et al. (11)
Allogeneic
40/F
AML
0 days
Cyclophosphamide, fludarabine, and anti-thymocyte globulin
L-AmB and 5-FC
Death
Chaaban et al. (current report)
Autologous
41/M
Non-Hodgkins T-cell lymphoma
9 days
BiCNU, etoposide, Ara-C, cyclophosphamide
L-AmB and 5-FC
Alive
1
Cases reported in Sun et al. (9). Ref., reference; F, female; ALL, acute lymphocytic leukemia; AmB, amphotericin B; FC, flucytosine; MM, multiple myeloma; Flu, fluconazole; AML, acute myeloid leukemia, L-AmB, liposomal amphotericin B; M, male.
Table 2
depletion of the T cells, while post-transplant regeneration and restoration of their cell-mediated immunity is a slow process and is often incomplete (9). It has been shown that patients could have low CD4 and CD8 counts for up to 10 years after an autologous SCT (10). Autologous HSCT patients are at greater risk than allogeneic HSCT recipients for cryptococcal disease. It is speculated that, in allogeneic SCT recipients, a strong T-helper 1 response, characterized by the production of proinflammatory cytokines, leads to a protective effect against Cryptococcus. In contrast, a dominant T-helper 2 phenotype, inducing interleukin 10, makes the autologous SCT recipients susceptible to cryptococcal disease (9). A review of US transplant centers, including 17,226 SOT patients and 16,390 HSCT from 2001 to 2005, revealed that Cryptococcus occurred in only 9% of the SOT patients and in 0% of the HSCT patients (9). Sun et al. (9) reported 9 cases of Cryptococcus in patients who received HSCT. Median time of onset was 64 days post transplant. Three meningitis cases were described; 2 of them after allogeneic SCT. Mendpara et al. (10) reported their case of cryptococcal meningitis, which occurred 4 months after autologous SCT in a multiple myeloma patient, with an end result of recovery after receiving medical treatment. Rimek et al. (11) reported a case of meningitis secondary to Cryptococcus adeliensis in a patient with acute myeloid leukemia undergoing allogeneic peripheral blood SCT. The patient received antifungal therapy with L-AmB and flucytosine, but died. Miniero et al. (12) reported a fatal case of cryptococcal meningitis in a 12-year-old girl with known acute lymphoblastic leukemia after autologous SCT, who received 13 days of AmB, flucytosine, and
granulocyte-macrophage colony-stimulating factor before her death (Table 2). Infection is usually fatal without therapy, and therefore prompt diagnosis and treatment are crucial (2). Our patient was started on fluconazole prophylaxis during his neutropenic phase and, despite adequate prophylaxis, he developed cryptococcal meningitis. Given the early onset on day 9 of HSCT, it is likely that the prior chemotherapy for T-cell lymphoma predisposed him to active fungal infection that may have been quiescent pre-transplant. This case highlights the virulence of Cryptococcus in the immunosuppressed patient. It also indicates the need to consider the diagnosis of fungal meningitis in patients with autologous HSCT who have CNS symptoms, irrespective of prophylaxis. Fluconazole prophylaxis might provide the clinician with a false sense of security against cryptococcal meningitis. If the diagnosis of cryptococcal meningitis is not entertained in a timely manner, the morbidity and mortality can be significantly increased.
Acknowledgements: Conflict of interest: None of the authors has any financial or other potential conflicts of interests. Funding: This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. Author contributions: S.C. prepared the manuscript and conducted the literature review. M.A. and L.J.W. contributed to the idea, critical review of the manuscript, and care of the patient.
Transplant Infectious Disease 2014: 0: 1–4
3
Chaaban et al: Cryptococcal meningitis post autologous SCT
References 1. Antony SJ, Patel A, Leonard J. Use of fluconazole in the treatment of non-AIDS cryptococcal meningitis. J Natl Med Assoc 1997; 89 (10): 694–695. 2. Lee SJ, Choi HK, Son J, Kim KH, Lee SH. Cryptococcal meningitis in patients with or without human immunodeficiency virus: experience in a tertiary hospital. Yonsei Med J 2011; 52 (3): 482–487. 3. Tjia TL, Yeow YK, Tan CB. Cryptococcal meningitis. J Neurol Neurosurg Psychiatry 1985; 48 (9): 853–858. 4. Orni-Wasserlauf R, Izkhakov E, Siegman-Igra Y, Bash E, Polacheck I, Giladi M. Fluconazole-resistant Cryptococcus neoformans isolated from an immunocompetent patient without prior exposure to fluconazole. Clin Infect Dis 1999; 29 (6): 1592–1593. 5. Jarvis JN, Harrison TS. HIV-associated cryptococcal meningitis. AIDS 2007; 21 (16): 2119–2129. 6. Kothavade RJ, Oberai CM, Valand AG, Panthaki MH. Disseminated cryptococcosis and fluconazole resistant oral candidiasis in a patient with acquired immunodeficiency syndrome (AIDS). J Infect Dev Ctries 2010; 4 (10): 674–678. 7. Hirai Y, Ainoda Y, Shoji T, et al. Disseminated cryptococcosis in a non-Hodgkin’s lymphoma patient with late-onset neutropenia
4
Transplant Infectious Disease 2014: 0: 1–4
8.
9.
10.
11.
12.
following rituximab-CHOP chemotherapy: a case report and literature review. Mycopathologia 2011; 172 (3): 227–232. Shih CC, Chen YC, Chang SC, Luh KT, Hsieh WC. Cryptococcal meningitis in non-HIV-infected patients. QJM 2000; 93 (4): 245–251. Sun HY, Wagener MM, Singh N. Cryptococcosis in solid-organ, hematopoietic stem cell, and tissue transplant recipients: evidence-based evolving trends. Clin Infect Dis 2009; 48 (11): 1566–1576. Mendpara SD, Ustun C, Kallab AM, Mazzella FM, Bilodeau PA, Jillella AP. Cryptococcal meningitis following autologous stem cell transplantation in a patient with multiple myeloma. Bone Marrow Transplant 2002; 30 (4): 259–260. Rimek D, Haase G, Luck A, Casper J, Podbielski A. First report of a case of meningitis caused by Cryptococcus adeliensis in a patient with acute myeloid leukemia. J Clin Microbiol 2004; 42 (1): 481–483. Miniero R, Nesi F, Vai S, et al. Cryptococcal meningitis following a thrombotic microangiopathy in an unrelated donor bone marrow transplant recipient. Pediatr Hematol Oncol 1997; 14 (5): 469–474.
Case report
Cryptococcal meningitis post autologous stem cell transplantation S. Chaaban, L.J. Wheat, M. Assi. Cryptococcal meningitis post autologous stem cell transplantation. Transpl Infect Dis 2014. All rights reserved Abstract: Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with nonHodgkin’s lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/lL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSF Cryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.
Cryptococcus neoformans is an encapsulated fungus known to cause a wide array of diseases ranging from colonization of the lungs to a more serious and deadly illness when it affects the central nervous system (CNS). It has been considered the most common cause of fungal-associated meningitis in both immunocompetent and immunocompromised individuals (1). Immunocompromised hosts include those with human immunodeficiency virus (HIV) infection, prolonged
S. Chaaban1, L.J. Wheat2, M. Assi3 1
Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, Kansas, USA, 2 MiraVista Diagnostics, Indianapolis, Indiana, USA, 3 Infectious Disease, Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, Kansas, USA
Key words: Cryptococcus; meningitis; autologous stem cell transplant; non-Hodgkins lymphoma Correspondence to: Maha Assi, MD, MPH, Infectious Disease, Department of Internal Medicine, University of Kansas School of Medicine-Wichita, 1010 North Kansas, Wichita, KS 67214, USA Tel: (316) 293-2650 Fax: (316) 293-1878 E-mail: [email protected]
Received 8 April 2013, revised 2 September 2013, 7 December 2013, accepted for publication 18 December 2013 DOI: 10.1111/tid.12216 Transpl Infect Dis 2014: 0: 1–4
treatment with glucocorticoids, organ transplantation, and malignancy (2). Prognosis is affected by the time interval between onset of symptoms to diagnosis and treatment (3). Fluconazole has been effective in treatment. Resistance has rarely been reported in an immunocompetent patient, but has been described in HIV-infected individuals (4). We present the case of a 41-year-old patient with peripheral T-cell non-Hodgkin’s lymphoma who developed Cryptococcus meningitis
1
Chaaban et al: Cryptococcal meningitis post autologous SCT
after autologous stem cell transplant (SCT) and while receiving fluconazole as prophylaxis.
Case presentation We present a 41-year-old man, known to be HIV negative, with peripheral T-cell non-Hodgkin’s lymphoma stage 4 B. He was initially treated with 3 cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) chemotherapy and then underwent autologous peripheral blood SCT with BEAC (BiCNU, etoposide, ARA-C, and cyclophosphamide) as the conditioning regimen. Transplant prophylaxis started on day 2 and consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, the patient developed headache with associated fever and change in mental status. His peripheral white blood cell count (WBC) then was 700/lL (4800–10,800/lL). Magnetic resonance imaging with contrast revealed both dural and cortical enhancement suggestive of meningoencephalitis. A lumbar puncture was performed and cerebrospinal fluid (CSF) analysis revealed a WBC of 39/mm3 (normal 0–10/mm3) with 77% lymphocytes, protein 63 mg/dL (normal 15–45 mg/dL), glucose 38 mg/dL (normal 40–70 mg/dL), CSF pressure 20.5 cmH2O (normal 9–18 cmH2O), and a positive cryptococcal antigen (Table 1). CSF culture confirmed Cryptococcus neoformans. The patient worked as an educator at a small community college, had no farming activity, and no other environmental exposures. The patient was treated with liposomal amphotericin B (L-AmB) 5 mg/kg intravenously daily and flucytosine 37.5 mg/kg per DobHoff tube every 6 h. Serial lumbar punctures were performed to decrease intracranial pressure and to follow CSF analysis (Table 1). The patient gradually became more awake and oriented, but did not recover his full mental abilities.
He was switched to fluconazole 400 mg daily after 3 weeks of AmB therapy, with sterilization of the CSF, and a negative CSF Cryptococcus antigen and culture. He was transferred to long-term care for nursing care and physical rehabilitation.
Discussion C. neoformans is a ubiquitous saprophyte that has been isolated from pigeon droppings, from heartwood of several tree species in South America and India, and from homes of HIV-infected African patients (5). This small encapsulated yeast usually enters the body via inhalation. Cryptococcus causes a mild pulmonary infection that, depending on the host immune system and the amount and virulence of the organism, could either be cleared, cause a latent infection, or disseminate (2, 5, 6). C. neoformans has the tendency to infect the CNS, thus leading to meningitis and meningoencephalitis (2). Cryptococcal infections constitute 2% of CNS infections in patients with an underlying hematological malignancy (7). Cryptococcus usually affects male patients more than female, in their third and fourth decades of life (8). Dissemination usually occurs in patients who have a defective T-cell immune system, mainly in patients with malignancy, on immunosuppressive medications, and in those who suffer from autoimmune disease, HIV infection, or sarcoidosis (5). It has been shown in Australia and the United States that 40.5–70.3% of patients have an underlying disease (8). Cryptococcus is considered to be the main cause of death secondary to mycosis in HIV-infected patients, thus stressing the role of cell-mediated immunity in eradication of the disease (6). Cryptococcus after hematopoietic SCT (HSCT) is a rare disease when compared with solid organ transplant (SOT). The proposed mechanism is that transplant-related antineoplastic agents lead to complete
Cerebrospinal fluid (CSF) test results Tests
Day 0
Day 1
Day 3
Day 12
Day 19
Day 41
CSF protein
63
65
49
31
CSF glucose
38
34
50
60
Negative
Negative
Negative
Negative
CSF cryptococcal antigen
1:64
1:64
Opening pressure (in H2O)
20.5 cm
21 cm
CSF fungal culture
Positive
Positive
1:128
Positive
Table 1
2
Day 5
Transplant Infectious Disease 2014: 0: 1–4
1:4 35 cm
20 cm
Negative
Negative
Chaaban et al: Cryptococcal meningitis post autologous SCT
List of similar cases of cryptococcal meningitis after stem cell transplantation in the literature1
Author (ref.)
Transplant source
Age/gender
Underlying condition
Onset
Conditioning regimen
Treatment
Outcome
Mineiro et al. (12)
Allogeneic
12/F
ALL
64 days
Total body irradiation, thiotepa, and cyclophosphamide
AmB and 5-FC
Death
Mendpara et al. (10)
Autologous
42/F
MM
4 months
Melphalan and cyclophosphamide
L-AmB, 5-FC, and Flu
Alive
Rimek et al. (11)
Allogeneic
40/F
AML
0 days
Cyclophosphamide, fludarabine, and anti-thymocyte globulin
L-AmB and 5-FC
Death
Chaaban et al. (current report)
Autologous
41/M
Non-Hodgkins T-cell lymphoma
9 days
BiCNU, etoposide, Ara-C, cyclophosphamide
L-AmB and 5-FC
Alive
1
Cases reported in Sun et al. (9). Ref., reference; F, female; ALL, acute lymphocytic leukemia; AmB, amphotericin B; FC, flucytosine; MM, multiple myeloma; Flu, fluconazole; AML, acute myeloid leukemia, L-AmB, liposomal amphotericin B; M, male.
Table 2
depletion of the T cells, while post-transplant regeneration and restoration of their cell-mediated immunity is a slow process and is often incomplete (9). It has been shown that patients could have low CD4 and CD8 counts for up to 10 years after an autologous SCT (10). Autologous HSCT patients are at greater risk than allogeneic HSCT recipients for cryptococcal disease. It is speculated that, in allogeneic SCT recipients, a strong T-helper 1 response, characterized by the production of proinflammatory cytokines, leads to a protective effect against Cryptococcus. In contrast, a dominant T-helper 2 phenotype, inducing interleukin 10, makes the autologous SCT recipients susceptible to cryptococcal disease (9). A review of US transplant centers, including 17,226 SOT patients and 16,390 HSCT from 2001 to 2005, revealed that Cryptococcus occurred in only 9% of the SOT patients and in 0% of the HSCT patients (9). Sun et al. (9) reported 9 cases of Cryptococcus in patients who received HSCT. Median time of onset was 64 days post transplant. Three meningitis cases were described; 2 of them after allogeneic SCT. Mendpara et al. (10) reported their case of cryptococcal meningitis, which occurred 4 months after autologous SCT in a multiple myeloma patient, with an end result of recovery after receiving medical treatment. Rimek et al. (11) reported a case of meningitis secondary to Cryptococcus adeliensis in a patient with acute myeloid leukemia undergoing allogeneic peripheral blood SCT. The patient received antifungal therapy with L-AmB and flucytosine, but died. Miniero et al. (12) reported a fatal case of cryptococcal meningitis in a 12-year-old girl with known acute lymphoblastic leukemia after autologous SCT, who received 13 days of AmB, flucytosine, and
granulocyte-macrophage colony-stimulating factor before her death (Table 2). Infection is usually fatal without therapy, and therefore prompt diagnosis and treatment are crucial (2). Our patient was started on fluconazole prophylaxis during his neutropenic phase and, despite adequate prophylaxis, he developed cryptococcal meningitis. Given the early onset on day 9 of HSCT, it is likely that the prior chemotherapy for T-cell lymphoma predisposed him to active fungal infection that may have been quiescent pre-transplant. This case highlights the virulence of Cryptococcus in the immunosuppressed patient. It also indicates the need to consider the diagnosis of fungal meningitis in patients with autologous HSCT who have CNS symptoms, irrespective of prophylaxis. Fluconazole prophylaxis might provide the clinician with a false sense of security against cryptococcal meningitis. If the diagnosis of cryptococcal meningitis is not entertained in a timely manner, the morbidity and mortality can be significantly increased.
Acknowledgements: Conflict of interest: None of the authors has any financial or other potential conflicts of interests. Funding: This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. Author contributions: S.C. prepared the manuscript and conducted the literature review. M.A. and L.J.W. contributed to the idea, critical review of the manuscript, and care of the patient.
Transplant Infectious Disease 2014: 0: 1–4
3
Chaaban et al: Cryptococcal meningitis post autologous SCT
References 1. Antony SJ, Patel A, Leonard J. Use of fluconazole in the treatment of non-AIDS cryptococcal meningitis. J Natl Med Assoc 1997; 89 (10): 694–695. 2. Lee SJ, Choi HK, Son J, Kim KH, Lee SH. Cryptococcal meningitis in patients with or without human immunodeficiency virus: experience in a tertiary hospital. Yonsei Med J 2011; 52 (3): 482–487. 3. Tjia TL, Yeow YK, Tan CB. Cryptococcal meningitis. J Neurol Neurosurg Psychiatry 1985; 48 (9): 853–858. 4. Orni-Wasserlauf R, Izkhakov E, Siegman-Igra Y, Bash E, Polacheck I, Giladi M. Fluconazole-resistant Cryptococcus neoformans isolated from an immunocompetent patient without prior exposure to fluconazole. Clin Infect Dis 1999; 29 (6): 1592–1593. 5. Jarvis JN, Harrison TS. HIV-associated cryptococcal meningitis. AIDS 2007; 21 (16): 2119–2129. 6. Kothavade RJ, Oberai CM, Valand AG, Panthaki MH. Disseminated cryptococcosis and fluconazole resistant oral candidiasis in a patient with acquired immunodeficiency syndrome (AIDS). J Infect Dev Ctries 2010; 4 (10): 674–678. 7. Hirai Y, Ainoda Y, Shoji T, et al. Disseminated cryptococcosis in a non-Hodgkin’s lymphoma patient with late-onset neutropenia
4
Transplant Infectious Disease 2014: 0: 1–4
8.
9.
10.
11.
12.
following rituximab-CHOP chemotherapy: a case report and literature review. Mycopathologia 2011; 172 (3): 227–232. Shih CC, Chen YC, Chang SC, Luh KT, Hsieh WC. Cryptococcal meningitis in non-HIV-infected patients. QJM 2000; 93 (4): 245–251. Sun HY, Wagener MM, Singh N. Cryptococcosis in solid-organ, hematopoietic stem cell, and tissue transplant recipients: evidence-based evolving trends. Clin Infect Dis 2009; 48 (11): 1566–1576. Mendpara SD, Ustun C, Kallab AM, Mazzella FM, Bilodeau PA, Jillella AP. Cryptococcal meningitis following autologous stem cell transplantation in a patient with multiple myeloma. Bone Marrow Transplant 2002; 30 (4): 259–260. Rimek D, Haase G, Luck A, Casper J, Podbielski A. First report of a case of meningitis caused by Cryptococcus adeliensis in a patient with acute myeloid leukemia. J Clin Microbiol 2004; 42 (1): 481–483. Miniero R, Nesi F, Vai S, et al. Cryptococcal meningitis following a thrombotic microangiopathy in an unrelated donor bone marrow transplant recipient. Pediatr Hematol Oncol 1997; 14 (5): 469–474.
