Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium

Abstract

Summary:Fifty patients affected by sickle cell anaemia underwent transplantation of HLA-identical haematopoietic stem cells (bone marrow, 48; cord blood, 2). Two groups of patients were considered for transplantation. Group 1 included 36 permanent residents of a European country who, retrospectively, met the inclusion criteria accepted at a consensus conference held in Seattle in 1990, wherein children were selected because they already had evidence of a morbid course. Group 2 included 14 patients who were transplanted earlier, had not received more than three blood transfusions and were transplanted because they had decided to return to their country of origin. Kaplan-Meier estimates of overall survival, event-free survival and disease-free survival at 11 years of the whole grafted population are 93, 82 and 85%, respectively. In group 1, overall survival, EFS and DFS were 88, 76 and 80% and in group 2, 100, 93 and 93%, respectively. Clinical manifestations of the disease, as well as disease associated haemolytic anaemia, disappeared in all successfully treated patients. Recovery of spleen function was present in seven out of 10 evaluated patients. Adverse events (death, absence of engraftment, mixed chimerism and relapse) occurred more frequently in group 1 than in group 2 (25% vs 7%, P Ͻ 0.001). Acute graft-versus-host disease (GVHD) was present in 20 patients (grade I or II, 19; grade III, 1), chronic GVHD in 10 (limited, 7; extensive, 3). One patient developed an acute myeloid leukaemia. Gonadal dysfunction was present in all patients (six boys and eight girls) transplanted close to or after puberty, although transient in one adolescent girl.

Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience

“…14 Multicenter trials have shown that about 20% of patients suffer from Xgrade II GVHD using a myeloablative conditioning regimen. [7][8][9] In our center's experience, 40% (4 out of 10 patients) had acute grade II GVHD although none of the patients had acute grade III/IV GVHD. Furthermore, 5 out of 10 patients suffered from chronic GVHD, which is higher than the 12-20% reported in multicenter trials.…”

“…[7][8][9] Seizure secondary to CSP with MRI changes suggestive of posterior leukoencephalopathy was commonly seen in our patients even with the use of anticonvulsant prophylaxis. A multicenter trial showed that 7 out of 16 patients with seizures had posterior leukoencephalopathy secondary to CSP toxicity suggesting that an alternative medication for GVHD prophylaxis should be considered.…”

“…[7][8][9] Important indications include stroke, history of recurrent hospitalizations or exchange transfusion for acute chest syndrome, and recurrent vaso-occlusive pain crisis (X 3 episodes per year).…”

Reconsideration of Age as a Contraindication for Curative Therapy of Sickle Cell Disease

“…The event-free survival and overall survival reported in this updated study of adults, aged 16 through 65 years, are comparable with those of matched sibling transplants in children with sickle cell disease, aged 2 through 22 years, receiving myeloablative conditioning regimens. [13][14][15] Importantly, both acute (0%) and chronic graft-vs-host disease (0%) were significantly lower than the rates reported for children (12.5%-40% and 40%, respectively). In addition, both morbidity and treatment-related mortality appear significantly less than those previously reported about children receiving matched-sibling transplants despite significantly greater fixed organ dysfunction and alloimmunization in these adult transplant recipients.…”

“…However, this cohort does represent an older group of patients with sickle cell disease who have significant premorbid conditions, and the patients tolerated the preparative regimen with engraftment rates similar to myeloablative regimens, even among children with sickle cell disease. [13][14][15] A subset of patients had donor CD3 chimerism of less than 50%, and these adults continued to take immunosuppression medications. When comparing the pretransplant medical regimen with posttransplant, these patients should still be experiencing a more positive experience.…”