Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Abstract

BackgroundParoxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hemopoietic stem cells for which the only curative treatment is allogeneic hematopoietic stem cell transplantation. Design and MethodsThe aim of this retrospective study was to assess the long-term clinical and hematologic results in 26 paroxysmal nocturnal hemoglobinuria patients who received hematopoietic stem cell transplantation in Italy between 1988 and 2006. The patients were aged 22 to 60 years (median 32 years). Twenty-three donors were HLA-identical (22 siblings and one unrelated) and 3 were HLA-mismatched (2 related and one unrelated). ResultsFifteen patients received a myeloablative conditioning consisting of busulfan and cyclophosphamide (in all cases from identical donor) and 11 were given a reduced intensity conditioning (8 from identical donor and 3 from mismatched donor). The cumulative incidence of graft failure was 8% (4% primary and 4% secondary graft failure). Transplant-related mortality for all patients was 42% (26% and 63% for patients transplanted following myeloablative or reduced intensity conditioning, respectively). As of October 31, 2009, 15 patients (11 in the myeloablative conditioning group and 4 in the reduced intensity conditioning group) are alive with complete hematologic recovery and no evidence of paroxysmal nocturnal hemoglobinuria following a median follow-up of 131 months (range 30-240). The 10-year Kaplan-Meier probability of disease-free survival was 57% for all patients: 65% for 23 patients transplanted from identical donor and 73% for 15 patients transplanted with myeloablative conditioning. No thromboembolic event nor recurrence of the disease were reported following transplant. ConclusionsThe findings of this study confirm that most patients with paroxysmal nocturnal hemoglobinuria may be definitively cured with hematopoietic stem cell transplantation.Key words: paroxysmal nocturnal hemoglobinuria, hematopoietic stem cell transplantation, conditioning regimen. Haematologica 2010;95:983-988. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Santarone S, Bacigalupo A, Risitano AM, Tagliaferri E, Di Bartolomeo E, Iori AP, Rambaldi A, Angelucci E, Spagnoli A, Papineschi F, Tamiazzo S, Di Nicola M, and Di Bartolomeo P. Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria

“…There are few reports on the use of SCT for PNH, and nearly all of them are based on small numbers of patients except two registry studies: one from the International Bone Marrow Transplant Registry (IBMTR) that included 57 patients 23 and one from an Italian group on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO), including 26 patients. 36 The main indications for transplantation in these and in our series were AA-PNH in about 50% of the cases. In our series, graft failure occurred in 6% of patients, a rate similar to that recently published by the GITMO.…”

“…In our series, graft failure occurred in 6% of patients, a rate similar to that recently published by the GITMO. 36 The place of a reduced intensity conditioning regimen in PNH, especially for patients with moderate organ dysfunction who may not tolerate a myeloablative regimen, is still unknown. In our study, 42 patients received a fludarabine-based reduced intensity conditioning regimen and showed no difference in terms of treatment-related mortality or OS (data not shown).…”

Allogeneic Hematopoietic Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria

“…Uni-variant analysis showed better outcome in younger patients (less than 30 years of age) and in patients transplanted less than 2 years from the date of diagnosis (Piccin A et al 2009). The GITMO (Gruppo Italiano Trapianto Midollo Osseo) has reported a retrospective study of 26 patients (median age 32 years) with PNH who received allo-HCT between 1988 and 2006 (Santaronr et al 2010). Median time from diagnosis to transplant was 33 months (range: 3-208 months).…”

Eculizumab before and after allogeneic hematopoietic stem cell transplantation in a patient with paroxysmal nocturnal hemoglobinuria

“…Eradication of the PNH clone has been achieved with both myeloablative and reduced-intensity conditioning regimens [8][9][10][11][12]. Transplant-related mortality in a recent study was 42% (26% and 63% for transplant patients following myeloablative and reduced intensity conditioning, respectively) [13].…”

“…While the optimal timing of transplantation may be changing in the era of eculizumab, the most effective conditioning regimen (myeloablative or reduced-intensity) is yet to be determined. The use of HSCT in the treatment of PNH has become less frequent now that there is an effective targeted therapy [13]. Eculizumab is a humanized monoclonal antibody that specifically binds to the C5 complement protein, preventing its cleavage to C5a and C5b, and therefore preventing formation of the membrane attack complex.…”