Bone marrow transplant cure for β-thalassaemia major: initial experience from a developing country

Ullah, Khalil; Khan, Badshah; Raza, Shahid; Ahmed, Parvez; Satti, Tariq Mahmood; Butt, Tariq M.; Tariq, Waheed Z.; Kamal, Muhammad Khalid

doi:10.1007/s00277-008-0478-8

Cited by 15 publications

(17 citation statements)

References 30 publications

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“…In selected regions of the world, the outcomes are outstanding when there is ready access to expanded supportive care services, with very few persons dying of thalassemia or of complications related to its treatment through the third and fourth decades of life. 12,20,21 In other areas of the world, however, supportive care measures are often difficult to access, which as predicted, has had a negative impact on survival. 39,40 We speculate that many of the transplant recipients included in this series lacked ready access to vital supportive care measures, such as regular iron chelation therapy, and there may have been delays in proceeding to transplantation in cases where resources were limited.…”

Section: Discussionmentioning

confidence: 97%

“…Using the risk features identified in the current analysis, it may be possible to assign a conditioning therapy that is better suited to those who are most in need of such modifications and in clinical settings where assigning a Pesaro risk classification is not possible. 7,12,22 We speculate that, for the diverse cohort in the current analysis, it may be appropriate to dispense with the Pesaro classification in high-risk patients and rely on this facile and novel risk assignment.…”

Section: Discussionmentioning

confidence: 99%

“…6 Most patient series outside Italy have observed comparatively worse outcomes after HLA-matched sibling BMT for thalassemia major. [12][13][14][15][16] Although the reasons for this disparity are unknown, there have been differences in recipient ethnicity, in the ability to assign a pretransplantation risk status, in how patients were prepared for transplantation, and in graft-versus-host disease (GVHD) prophylaxis, which might account for the disparate outcomes. There is also the possibility of a center effect, which might have contributed to an apparent poorer outcome in the smaller patient series outside Italy.…”

Section: Introductionmentioning

confidence: 99%

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HLA-matched sibling bone marrow transplantation for β-thalassemia major

Sabloff

Chandy

Wang

et al. 2011

Blood

119

113

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We describe outcomes after human leukocyte antigen-matched sibling bone marrow transplantation (BMT) for 179 patients with ␤-thalassemia major. The median age at transplantation was 7 years and the median follow-up was 6 years. The distribution of Pesaro risk class I, II, and III categories was 2%, 42%, and 36%, respectively. The day 30 cumulative incidence of neutrophil recovery and day 100 platelet recovery were 90% and 86%, respectively. Seventeen patients had graft failure, which was fatal in 11. Six of 9 patients with graft failure are alive after a second transplantation. The day 100 probability of acute graft-versus-host disease and 5-year probability of chronic graftversus-host disease was 38% and 13%, respectively. The 5-year probabilities of overall-and disease-free survival were 91% and 88%, respectively, for patients with Pesaro risk class II, and 64% and 62%, respectively, for Pesaro risk class III. In multivariate analysis, mortality risks were higher in patients 7 years of age and older and those with hepatomegaly before BMT. The leading causes of death were interstitial pneumonitis (n ‫؍‬ 7), hemorrhage (n ‫؍‬ 8), and veno-occlusive disease (n ‫؍‬ 6). Proceeding to BMT in children younger than 7 years before development of end-organ damage, particularly in the liver, should improve results after BMT for ␤-thalassemia major. (Blood. 2011;117(5):1745-1750)

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HLA-matched sibling bone marrow transplantation for β-thalassemia major

Sabloff

Chandy

Wang

et al. 2011

Blood

119

113

View full text Add to dashboard Cite

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“…11 Subsequently, several centers worldwide have started their own transplant programs. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Recent results show that, with modern transplantation approaches, and careful patient selection, even better results could be obtained (Table 2). At the same time, however, survival without transplantation of TM patients has improved as the result both of a better understanding of the pathophysiology of iron overload and improvements in the medical therapy of TM; survival into the fourth or fifth decade of life is now possible for well-treated patients.…”

Section: Hsct In Children and Adolescentsmentioning

confidence: 99%

Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

et al. 2014

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“…2,3 The results of HLA-matched sibling BMT for thalassemia major of the patient series outside Italy were not as successful, but the reasons for this were obscure when compared. [4][5][6][7] In a recent report, 179 patients with β-thalassemia major who received BMT from HLA-matched sibling were reviewed. The distribution of Pesaro risk class I, II, and III categories was 2%, 42%, and 36%, respectively.…”

Section: Introductionmentioning

confidence: 99%

Overview of the Current Issues and Advances in Haemopoietic Stem Cell Transplantation for β-thalassemia Major

Anak¹

2011

Thalassemia Reports

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Bone marrow transplantation (BMT) is the only possible curative treatment for β-thalassemia major. The largest experience occurred in Pesaro, Italy, where the BMT was applied after a standard risk assessment. The patients were divided into 3 risk classes based on liver size by physical examination, the presence or absence of fibrosis by liver biopsy, and adherence to regular iron chelation. Outcomes were mainly affected by the risk status. After modifications to the conditioning regimens, the risk of transplantation-related complications in highrisk recipients reduced considerably. As a result, outcomes after transplantation have become more similar across risk categories. For BMT, most centers use bone marrow instead of peripheral blood in thalassemia. Some studies showed that peripheral blood stem cell transplantation (PBSCT) is better than BMT with regard to hematologic recovery, hospitalization period, leukemia-free survival, overall survival (OS), and transplant-related mortality (TRM). No significant differences were seen in grade II to IV acute GVHD (aGVHD); but the incidence of chronic GVHD (cGVHD) was significantly higher in the PBSCT group. BMT from unrelated donors may offer similar results to those obtained using HLA-identical family donors, at least for patients who are not fully compliant with conventional treatment and do not yet show severe complications of iron overload. All studies conclude that MUD BMT might be a good alternative for patients with less risk factors. Another study concluded that, at present, due to high graft failure and GVHD rates, BMT from alternative donors should be restricted to patients who have poor life expectancies because they cannot receive adequate conventional treatment or because of alloimmunization to minor blood antigens. In another study unrelated cord blood transplantation (CBT) was compared to related donor transplantation for children with β-thalassemia. The results were comparable to the survival rates of related-donor BMT for thalassemia. It has always been a dream for parents to have a new baby who might be a donor for his/her sibling and save his/her life. Today some families tried to learn the HLA group of the fetus using prenatal diagnosis. The last step in this development was preimplantation genetic diagnosis (PGD). PGD has become available as an alternative to prenatal diagnosis in order to avoid the risk for pregnancy termination, because PGD allows selection of unaffected embryos before a pregnancy is established. Gene therapies, the ultimate idea, involves replacing allogeneic stem cell transplantation with the transfer of normal globin genes into patientderived autologous haematopoietic stem cells, bypassing the need for allogeneic donors and the immunosuppression required to achieve engraftment of the transplanted cells and to eliminate the risk of donor-related graft-versus-host disease. The successful preclinical studies in thalassaemia mousemodels, the accumulating data on lentiviral vector-mediated HSC transduction and the anticipated increased safety of lineage-restricted globin SIN lentiviral vectors strongly support the initiation of Phase I gene therapy clinical trials in β-thalassaemia.

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Bone marrow transplant cure for β-thalassaemia major: initial experience from a developing country

Cited by 15 publications

References 30 publications

HLA-matched sibling bone marrow transplantation for β-thalassemia major

HLA-matched sibling bone marrow transplantation for β-thalassemia major

Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

Overview of the Current Issues and Advances in Haemopoietic Stem Cell Transplantation for β-thalassemia Major

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