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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2006  |  Volume : 17  |  Issue : 4  |  Page : 564-567
Bone Marrow Transplantation for Leukocyte Adhesion Deficiency-I: Case Report


Bone Marrow Transplantation Unit, King Hussein medical center, Royal Medical Services,Amman, Jordan

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   Abstract 

Leukocyte adhesion deficiency type I (LAD-I) is a rare autosomal recessive immunodeficiency syndrome leading to recurrent bacterial and fungal infections. Bone marrow transplantation offers the only cure. In this report, we describe the course and outcome of bone marrow transplant in a 4 month-old female infant with LAD-I at King Hussein Medical Center, Jordan. A successful matched HLA- related allogeneic bone marrow transplantation was performed. Engraftment was demonstrated on the 12 th day. The patient developed Grade III grafts versus host disease (GVHD), veno-occlusive disease of the liver, and late onset hemorrhagic cystitis. She recovered with appropriate immune reconstitution.

Keywords: Leukocytes, Adhesion, Immunodeficiency, Congenital, Bone Marrow, Transplant, Jordan.

How to cite this article:
Al-wahadneh AM, Haddadin I, Hamouri M, Omari K, Aejellat F. Bone Marrow Transplantation for Leukocyte Adhesion Deficiency-I: Case Report. Saudi J Kidney Dis Transpl 2006;17:564-7

How to cite this URL:
Al-wahadneh AM, Haddadin I, Hamouri M, Omari K, Aejellat F. Bone Marrow Transplantation for Leukocyte Adhesion Deficiency-I: Case Report. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2019 Nov 18];17:564-7. Available from: http://www.sjkdt.org/text.asp?2006/17/4/564/32496

   Introduction Top


Leukocyte adhesion deficiency type I (LAD I) is an autosomal recessive immuno­deficiency syndrome.[1] It results from the failure of CD18 expression (aM Q 2 and EL), an integrin that serves as the receptor for C3b on myeloid and lymphoid cells. [1],[2] It occurs in the absence of or reduced membrane expression of leukocyte-associated integrins, lymphocyte function-associated antigen I (LFA-I; CD11a-CD18), Mac-1 (CD11b-CD18), and p150-95 (CD11c-CD18). [3] It affects about 1 in 10 6 of the population and has been re­ported in less than 200 patients throughout the literature.[4]

LAD I is characterized by delayed separation of the umbilical cord, recurrent episodes of sepsis, skin infection as well as gingival and periodontal disease. [5] Most patients with this disease have marked leukocytosis and succumb to infection commonly before the age of two years [6] The most common infectious agents are Staphylococcus species, enteric gram­negative bacteria and fungal organisms. [7]

Bone marrow and other modes of stem cell transplantation are gold-standard therapies and have a very high success rate. [8] Various other types of intervention for LAD-I have included prophylactic antibiotics, interferon­gamma and leukocyte transfusions; none has shown significant benefit. [6],[7]

To the best of our knowledge, this report provides the first description of a successful bone marrow transplant (BMT) in a patient with LAD-I at King Hussein Medical Center (KHMC) in Jordan.


   Case Report Top


A 7 month-old female was diagnosed with LAD-I at the age of 4 months. She was a product of a full term normal vaginal delivery to first-degree related parents. Since the age of 2 weeks, she was frequently admitted for Staphylococcal aureus sepsis, hepatospleno­megaly, oral candidal thrush and poor weight gain. Her umbilical cord separated at the 2nd week of age. She did not have skin lesions or abscesses. Her family history was unremarkable.

Laboratory data showed high leukocyte counts (59,000/mm 3) associated with neutro­philia. The flowc ytometric analysis of peri­pheral blood neutrophiles revealed a complete absence of CD18/CD11b and CD18/CD11c integrin proteins. The T- and B- cell lympho­cytes, serum immunoglobulin assay, liver and kidney functions were normal apart from mildly elevated liver enzymes. Staphylococcal aureus was isolated from blood cultures on 3 occasions. A chest X-ray showed bilateral inflammatory shadows.

She was treated with repeated courses of different antibiotic combinations including cloxacillin, sulphamethoxazole-trimethoprium, impipenem, ciprofloxacillin, vancomycin and amikacin with amphotericin B and itracona­zole with temporary responses.

Because of the poor response to conven­tional treatment, we contemplated bone marrow transplantation (BMT) as the only cure. Before transplantation, the patient was assessed by chest x-ray, computed axial tomography (CT) of the chest and abdomen and hepatic and portal vein Doppler study. Other investigations included albumin, alkaline phosphatase, bilirubin, a-glutamyl transferase, and aspartate aminotransferase. Broncho­alveolar lavage was not performed.

Age at transplantation was 4 months. The donor was the patient's 5 year-old brother who was O +ve similar to the patient. The donor was completely HLA-matched with the patient (HLA: A3, A11: B16, B49 (21): Cw7: DR7, DR17 (3): broad specific DR52).

The patient was isolated and received intra­venous sulphamethoxazole-trimethoprium (10 mg/kg/day) for anti-pneumocystis carnii prophylaxis, itraconazole (5 mg/kg/day) at day-1 for antifungal- prophylaxis. Intravenous immunoglobulin (IVIG) (0.5 g/kg weekly) and aciclovir (500mg/m 2 ) was administered at day -1 for anti-viral prophylaxis. The patient also received prophylaxis therapy for graft versus host disease (GVHD).

A double lumen central venous line was inserted at day -15 (prior to the transplant­ation). Oral Epanutin (5 mg/kg/day) and ursodeoxycholic acid (7 mg/kg tds) were given at day -11. During days -9 to -6, oral busulphan (4 mg/kg/day) was administered. Day - 5 was a rest day. The patient received intravenous cyclophosphamide (50mg/kg/day) with a bolus (25mgs/kg), followed by main­tenance (60 mgs/kg) infusions, and hydration (3000 ml/m 2 /day of glucose 5%/0.45 saline +20 mmols of KCL) during days -4 to -2. Intravenous cyclosporin (2.5 mg/kg BD) was started on day -1.

The donor bone marrow was harvested at day zero. A total of 115 cc (total WBC: 45x 10 6, mononuclear cells: 2.9 x 10 8 ) of bone marrow was harvested and infused into the patient. There was evidence of engraftment at day 12 post transplantation.

The patient developed grade III acute skin and gut GVHD at day +4, treated with high dose methylprednisolone (30 mg/kg/day) for 3 days and maintained on (5 mg/kg/day) for 2 weeks. At day + 7, the patient developed veno-occlusive disease of the liver (VOD) resulting in a 2 kg weight gain over 5 days, severe ascitis, hepatomegaly, hyperbilirubi­nemia (22 mg%) and mild renal impairment. The patient was treated with low-molecular weight heparin (Clexan), fresh-frozen plasma, platelet infusions to maintain platelet levels above 30.000/mm 3 , packed red blood cells to maintain packed cell volume (PCV) above 25%, and diuretics. The patient developed moderate hemorrhagic cystitis at day +31 for which she was treated with irrigation, hydration and diuresis. The patient completely recovered at day +60 and began to tolerate oral feeding and was dischraged home on oral medications. Follow up at +18 and +60 showed 100% expression of CD18/CD11b, CD18/CD11c on peripheral blood neutrophiles, respectively.


   Discussion Top


In our case, the patient presented with findings compatible with LAD I syndrome of a severe phenotype. Her presentation included recurrent staphyloccocal sepsis, hepatospleno­megaly, poor weight gain, neutrophilic leuko­cytosis and complete absence of CD11/CD18 expression. LAD-I usually predisposes patients to severe bacterial infections that result in death within the first years of life. [1],[2],[3] The outcome of LAD-I remains poor with conventional management. [4]

Worldwide survey of BMT in immunodefi­ciency diseases (1968-1997) reported 23 successful transplantations out of 32. [8] However, BMT is risky because of the pre­transplantation chemotherapy or pre-existing liver or lung disease. The bone marrow in patients with LAD, as in other inherited dis­orders of the myeloid-macrophage lineage, is hyperactive. This requires the use of an aggressive myelo-ablative condoitinoning regimen in order to overcome graft rejection and facilitate engraftemnet. [9]

In previous reports, engraftment was demon­strated between day +13 and +95, but in our case neutrophil recovery was demonstrated as early as day +12. The reduced ability of patients with a severe form of LAD to reject marrow grafts appears to significantly faci­litate engraftment. [8],[11] This advantage is, however, partly counterbalanced by an increased risk of GVHD, [8] as our patient demonstated. However, her disease was transient and responded to treatment.

Pre-existing liver disease appears to be a greater risk factor than suboptimal donor matching. [8],[9] Our patient developed hepato­megaly with elevated liver enzymes before transplantation and this may explain the occurrence of moderately severe VOD, which responds well to our treatment measures.

Despite the occurrence of severe bacterial infections before BMT, there have been no infectious complications six months post­BMT in our patient. [10]

 
   References Top

1.Thomas C, Le deist F, Cavazzana-Calvo M, et al. Results of Allogeneic bone marrow transplanation in patients with leukocyte adhesion deficiency. Blood 1995;86(4):1629-35.  Back to cited text no. 1    
2.Mancias C, Infante AJ, Kamani NR. Matched unrelated donor bone marrow transplantation in leukocyte adhesion deficiency. Bone Marrow Transplantation, 1999;24:1261-3.  Back to cited text no. 2    
3.Sabatino G, De Martino M, Chiarelli F, Paciocco D, Amerio G. Leukocyte adhesion deficiency disorder in an infant. Int J Immunopathol Pharmacol 1999;12(3): 139-42.  Back to cited text no. 3    
4.Jamal T, Barbouche MR, Ben Hariz M, Bejaaoui M, Fathallah MD, Dellagi K. Genetic and immunological assessment of a bone marrow transplantation in a patient with a primary immune defect: leukocyte adhesion deficiency. Arch Inst Pasteur Tunis. 1998;75(3-4):177-83.  Back to cited text no. 4    
5.Etzioni A,Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CI, Puck JM, ed. Primary immuno­deficiency disease: Amolecular and genetic approach. 1st ed.New York: Oxford University Press.  Back to cited text no. 5    
6.Al-tekriti N, Ramadan D, Aboobacker K. Leukocyte adhesion deficiency type 1 in a bedouin child: first reported case from Kuwait. Kuwait Med J 2001;33(1):65-7.  Back to cited text no. 6    
7.Kilic SS. leukocyte adhesion deficiency in a case presentiong as a septic arthritis. Int Pediatr 2002;17(2):96-7.  Back to cited text no. 7    
8.Buckley RH, Fischer A. Bone marrow transplantation for primary immunodefi­ciency diseases. In: Ochs HD, Smith CI, Puck JM, ed. Primary immunodeficiency disease: Amolecular and genetic approach. 1st ed.New York:Oxford University Press.  Back to cited text no. 8    
9.Hung CH, Cheng SN, Hua YM, Wang CL, Chen YH, Young KD. Leukocyte adhesion dfeiciency disorder: report of one case. Acta Paediatr Taiwan 1999;40(2):128-31.  Back to cited text no. 9    
10.Farinha NJ, Duval M, Wagner E, et al. Unrelated bone marrow tramsplanation for leukocyte adhesion deficiency. Bone marrow transplant 2002;30(12):979-81.  Back to cited text no. 10    
11.Stary J, Kobylka P, Vavra V, et al. Successful transplantation of fetal blood in a boy with leukocyte integrin deficiency syndrome. Cas Lek Cesk 1996;135(21):695-8.  Back to cited text no. 11    

Top
Correspondence Address:
Adel Mohammed Al-wahadneh
Pediatric Immunologist, Pediatric Department King Hussein Medical Center, Royal Medical Services, P.O.Box 150 719, Amman 11115
Jordan
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PMID: 17186693

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    Abstract
    Introduction
    Case Report
    Discussion
    References
 

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