A 12-year-old girl was diagnosed with thalassemia major. A 12-year-old girl with Ã-thalassemia hemoglobin E dis- ease received a marrow transplant from her ...
Bone Marrow Transplantation, (1997) 19, 1259–1260 1997 Stockton Press All rights reserved 0268–3369/97 $12.00
Case report Malaria infection after allogeneic bone marrow transplantation in a child with thalassemia V-B Tran1 , V-B Tran1 and K-H Lin2 1
Blood Transfusion and Hematology Center, Hochiminh City; Department of Hematology, Hochiminh Medical School, Vietnam; and Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan
2
Summary:
Case report
A 12-year-old girl with b-thalassemia hemoglobin E disease received a marrow transplant from her HLA-identical elder brother in July 1995. She had previously been treated by repeated blood transfusions. Conditioning included busulfan 16 mg/kg for 2 days and cyclophosphamide 120 mg/kg for 2 days. Cyclosporine was used for graft-versus-host disease prophylaxis. Spiking fevers occurred on days 6 and 11. Plasmodium falciparum parasites, both trophozoites and gametocytes, were found on the peripheral blood smear. Quinine 30 mg/kg three times a day for 7 days followed by a single dose of mefloquine 25 mg/kg was given. The fever subsided within 2 days and parasitemia cleared in 4 days. After transplant, the girl autologously reconstituted and was followed-up over 15 months. Keywords: malaria; allogeneic BMT; thalassemia
A 12-year-old girl was diagnosed with thalassemia major at the age of 8 years (HbA 0%, HbE 55%, HbF 45%). She was of short stature (height 124 cm, weight 21 kg) and had pallor, facial and skull bony deformities, fatigue, huge spleen, and enlarged liver. Elevation of serum ferritin and liver enzymes was also noted. The average hemoglobin level was around 3–7 gm/dl. Regular blood transfusion was needed to keep the Hb around 10 gm/dl. One month before BMT, splenectomy was carried out with no significant improvement in blood transfusion requirements. She also had cardiomegaly and tachypnea. Intensive blood transfusion was given during the last month before BMT. In total, eight packed red cell transfusions were given, the last on day 24. The donor was her elder brother, aged 16 years, with an identical HLA type, and the same RBC blood group. Conditioning included oral busulfan 16 mg/kg for 2 days and intravenous cyclophosphamide 120 mg/kg for 2 days with adequate hydration and 150% 2-mercaptoethane-sulfonate. The marrow dose was 8.5 3 108 nucleated cells/kg of patient body weight. Cyclosporine was used for graftversus-host disease prophylaxis. An absolute neutrophil count of over 500/mm 3 occurred on day 11, and a platelet count of over 25 000/mm3 on day 28. Platelet transfusions were given during the thrombocytopenic period. Fever developed on day 6 followed by another spike on day 11 when Plasmodium falciparum was found on the routine blood smear. Trophozoites and few gametocytes (28 parasites/1000 RBC) were seen (Figure 1). Quinine 30 mg/kg i.v. three times a day for 7 consecutive days followed by a single dose of mefloquine 25 mg/kg was given. Improvement was dramatic and the fever subsided on day 16. Parasitemia cleared on day 15. There was no relapse for over 15 months despite several other RBC and platelet transfusions (all blood products given were irradiated 25 Gy and white cell filtered). None of the blood donors nor the patient, followed every 2 months clinically and examined for malaria parasites by the Quick-BufferCoat fluorescence technique (QBC test-kit; Becton Dickinson, Mountain View, CA, USA) had evidence of malaria infection. After transplant, the girl was still transfusion dependent
Infection frequently occurs as a consequence of bone marrow transplantation (BMT), related to the process of marrow ablation which results in neutropenia and immune deficiency. Bacterial and fungal infections are usual during the immediate post-BMT period, and subsequently viral infections or reactivations are more frequent, such as cytomegalovirus or herpes zoster.1 The transmission of malaria by BMT was reported in 1986. A 27-year-old Nigerian woman with aplastic anemia had a febrile episode on day 6 after BMT and Plasmodium falciparum infection was documented on blood films. Effective therapy could not be administered as death occurred.2 We experienced a case of malaria transmitted during BMT and outline the successful measures used to prevent transmission of malaria and to treat the infection during BMT. These measures are important in countries inside the tropical malaria endemic areas including Vietnam which is just beginning a BMT program.
Correspondence: Dr K-H Lin, Department of Pediatrics, National Taiwan University Hospital, No. 7, Chungshan South Road, Taipei, Taiwan Received 25 November 1996; accepted 27 February 1997
Malaria infection after BMT in thalassemia V-B Tran et al
1260
Parasitemia (/1000 RBC) Temperature
39
38
Fever (°C)
30
BMT 20
Last 37 transfusion 10
Plasmodium falciparum 36 –4
–2
0
+2
+4
+6
+8 +10 +12 +14 +16
Days Temperature (°C) Parasites/1000 RBC
Quinine i.v. Mefloquine (30 mg/kg (25 mg/kg) three times a day)
Figure 1 A 12-year-old girl with b-thalassemia hemoglobin E disease had a spiking fever on day 6 after marrow transplantation and a heavy Plasmodium falciparum parasitemia was detected on day 11 which responded dramatically to quinine therapy.
and still had hepatomegaly. Chromosome studies and genetic analyses were not performed until 15 months after transplant which showed female karyotype and 41/42 (-TTCT) deletion plus E mutation.
However, this is less likely in Hochiminh City than in rural areas. As there is a potential risk of transmission of malaria to both donor and recipient in malarious areas, both donors and recipients in these areas should receive a therapeutic course of quinine or chloroquine prior to BMT. All blood donors should receive similar treatment. In endemic areas, spikes of fever should always lead to a blood film check. In this case, the classical quinine antimalaria management had a dramatic effect despite the heavy parasitemia. The mefloquine given with the aim of preventing relapse was also successful for at least 15 months after BMT. This management seems to be appropriate but needs further verification. Conditioning regimen was designed to avoid the risk of fatal infection, but it also increased the risk of rejection. The girl may have died of Plasmodium infection if the conditioning was intense enough to ensure engraftment. Marrow engraftment jeopardised by malaria infection has not been previously recognized in man. However, susceptibility of multipotent haemopoietic stem cell deficient W/W2 mice to Plasmodium berghei infection has been noted.4 The thalassemic haemopoietic stem cell may be more resistant to malaria infection than the normal donor haemopoietic stem cells,5 and the rapid autologous recovery after BMT during the period of malaria infection in this case ensured survival. Acknowledgements This study was supported in part by the National Health Department, National Taiwan University Hospital, Sandos Pharmaceutical Co. and Kirin Pharmaceutical Co.
Discussion Vietnam is in an endemic malaria area and the first three allogeneic BMTs were performed in July 1995. One thalassemic patient had a malaria infection in the post-transplant period The origin of the parasitemia may have been from one of the many blood units given before BMT since the incubation time of malaria can be from 1 to 3 weeks. Although the screening of donors did not give positive results, this possibility could not be ruled out since normal carriers can be asymptomatic in endemic areas. Acquired immunity to malaria parasites in endemic areas leads to absence of detectable parasitemia but an inability to completely eradicate the infection, a phenomenon that has been called premunition.3 The other origin of infection could have been from mosquito bites during her stay in hospital or at home.
References 1 Lin KH, Lee MJ, Hwang KC et al. Infections in marrow transplant recipients. J Formosan Med Assoc 1988; 87: 721–727. 2 Dharmasena F, Gordon-Smith EC. Transmission of malaria by bone marrow transplantation. Transplantation 1986; 42: 228. 3 Sergent E. Latent infection and premunition: some definitions of microbiology and immunology. In: Garnham PCC, Price AE, Roitt IM (eds). Immunity to Protozoa. Blackwell: Oxford, 1963, p 38. 4 Asami M, Owhashi M, Abe T, Nawa Y. Susceptibility of multipotent haemopoietic stem cell deficient W/W2 mice to Plasmodium berghei infection. Immunol Cell Biol 1991; 69: 355–360. 5 Modell B, Berdoukas V. Genetics and thalassemia. The Clinical Approach to Thalassemia. Grune & Stratton: London, 1984, pp 4–16.
