Abstract

Allogeneic hematopoietic stem cell transplantation is the only potentially curative treatment for the bone marrow dysfunction seen in patients with Shwachman-Diamond Syndrome (SDS). Historically, these patients have fared poorly with intensive conditioning regimens with increased regimen-related toxicity especially involving the heart and lungs. We report our institutional experience with a reduced intensity conditioning protocol in 7 patients with SDS and bone marrow aplasia or MDS/AML. Patient demographics are summarized in Table 1 below. The preparative regimen consisted of Campath-1H for 4 successive days (day -22 to day -19), Fludarabine 30 mg/m2/day for 5 days (Day - 8 to day -4) followed by Melphalan 140 mg/m2 for 1 day (day -3). Four patients received matched related marrow, 2 received matched unrelated peripheral blood stem cells (PBSC) and 1 received matched unrelated marrow. All but one were 8/8 allele HLA matched. Graft-versus-host disease (GVHD) prophylaxis consisted of Cyclosporine(CSA) and Methotrexate in all except one patient who received tacrolimus and mycophenolate mofetil as she was CSA intolerant. All patients established 100% donor-derived hematopoiesis. No major regimen related toxicity was seen except hyperglycemia requiring insulin in one patient and Grade II renal insufficiency in 1 patient which resolved with conservative management. Transplant outcomes are described in Table 2. These data indicate that HSCT with reduced intensity conditioning is feasible in patients with SDS and associated with excellent hematopoietic recovery and modest morbidity.

Table 1.

Patient Demographics

Patients#1#2#3#4#5#6#7
Age(yrs) 10 12 29 
Gender Male Male Male Male Male Female Female 
SBDS mutation 183_184 TA to CT 183_184 TA to CT K62X 183_184 TA to CT 183_184 TA to CT IVS2+2 T to C 183_184 TA to CT 
        
        
Clinical status Transfusion dependence, recurrent infections Cytopenias Cytopenias Dysplasia Cytopenias Acute myeloid leukemia Dysplasia, Cytopenias 
        
Marrow cytogenetics del20q12 and del7q31 i(7)(q10) del20q12 del20q12 del20q12 Complex karyotype including monosomy 7,del5q Normal 
Patients#1#2#3#4#5#6#7
Age(yrs) 10 12 29 
Gender Male Male Male Male Male Female Female 
SBDS mutation 183_184 TA to CT 183_184 TA to CT K62X 183_184 TA to CT 183_184 TA to CT IVS2+2 T to C 183_184 TA to CT 
        
        
Clinical status Transfusion dependence, recurrent infections Cytopenias Cytopenias Dysplasia Cytopenias Acute myeloid leukemia Dysplasia, Cytopenias 
        
Marrow cytogenetics del20q12 and del7q31 i(7)(q10) del20q12 del20q12 del20q12 Complex karyotype including monosomy 7,del5q Normal 
Table 2.

Transplant outcomes Patients

Patients#1#2#3#4#5#6#7
Days to myeloid engraftment 15 12 15 11 14 14 13 
Platelet Recovery(days) 27 39 33 18 68 14 not engrafted 
Donor Chimerism 100% 100% 100% 100% 100% 99.8% 100% 
Hospital stay(days) 29 32 35 28 29 22 46 
Length of follow-up(days) 758 723 679 385 218 65 33 
Acute GVHD Gd II skin None None None None Gd I skin None 
Lansky scale 100% 100% 100% 100% 100% 90% 60% 
Patients#1#2#3#4#5#6#7
Days to myeloid engraftment 15 12 15 11 14 14 13 
Platelet Recovery(days) 27 39 33 18 68 14 not engrafted 
Donor Chimerism 100% 100% 100% 100% 100% 99.8% 100% 
Hospital stay(days) 29 32 35 28 29 22 46 
Length of follow-up(days) 758 723 679 385 218 65 33 
Acute GVHD Gd II skin None None None None Gd I skin None 
Lansky scale 100% 100% 100% 100% 100% 90% 60% 

Author notes

Disclosure: No relevant conflicts of interest to declare.