Successful application of nonmyeloablative transplantation for paroxysmal nocturnal hemoglobinuria.
OBJECTIVE
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder that manifests as hemolytic anemia, venous thrombosis, and deficient hematopoiesis. Although allogeneic hematopoietic stem cell transplantation is considered the only curative therapeutic measure, transplant-related mortality is not negligible. Several studies supported the use of nonmyeloablative stem cell transplantation (NST) for patients of advanced age or with organ dysfunction. Hence, we used NST in a PNH patient who suffered from acute renal failure due to repeated episodes of hemolysis.


METHODS
We performed NST using a conditioning regimen consisting of cladribine 0.11 mg/kg x 6, busulfan 4 mg/kg x 2, and rabbit anti-thymocyte globulin 2.5 mg/kg x 2. He received peripheral blood stem cells from his human leukocyte antigen-matched brother. Prophylaxis against graft-vs-host disease was performed with cyclosporine A alone. Chimerism of peripheral blood mononuclear cells was evaluated serially using short tandem repeat analysis and flow cytometry.


RESULTS
No meaningful regimen-related toxicities were documented. Donor chimerism of 90 to 100% was achieved on day 14 and thereafter. The patient is doing well, without any recurrence of hemolysis 6 months after transplant. Follow-up chimerism studies confirmed stable and functioning donor-type hematopoiesis.


CONCLUSIONS
NST may become a safe and curative approach in patients with PNH. Further studies are needed to establish the role of NST for treatment of PNH.
Suenaga
K
K
Stem Cell Transplant Unit, National Cancer Center Hospital, Tokyo, Japan.
Kanda
Y
Y
Niiya
H
H
Nakai
K
K
Saito
T
T
Saito
A
A
Ohnishi
M
M
Takeuchi
T
T
Tanosaki
R
R
Makimoto
A
A
Miyawaki
S
S
Ohnishi
T
T
Kanai
S
S
Tobinai
K
K
Takaue
Y
Y
Mineishi
S
S
D000961:Antilymphocyte Serum; D002066:Busulfan; D017338:Cladribine; D016572:Cyclosporine / Q000627:therapeutic use; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006457:Hemoglobinuria, Paroxysmal / Q000628:therapy*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D017338:Cladribine; D016572:Cyclosporine; D002066:Busulfan