Successful haploidentical hematopoietic stem cell transplantation for Glanzmann’s thrombasthenia: First report from northern India

INTRODUCTION

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder caused by quantitative or qualitative defects in the platelet glycoprotein IIb/IIIa complex.^[1,2] This integrin plays a central role in fibrinogen binding and platelet aggregation, and its absence leads to defective primary hemostasis. Clinically, patients present from childhood with recurrent epistaxis, gum bleeding, easy bruising and, in females, menorrhagia. Severity varies, but some children develop life-threatening hemorrhage and remain dependent on supportive transfusions.

Platelet transfusion is the cornerstone of acute management, but with repeated exposure, alloimmunization is common. Once antibodies develop against platelet glycoproteins or human leukocyte antigens (HLAs), transfusion support becomes ineffective. Recombinant factor VIIa offers temporary hemostatic benefit but is not curative. In contrast, hematopoietic stem cell transplantation (HSCT) offers definitive correction of the underlying defect, restoring normal megakaryocyte function.

Published literature describes successful HSCT in GT, mostly from matched sibling donors. However, many patients, especially in low- and middle-income countries, lack matched donors or access to registries. Haploidentical HSCT increases donor availability but carries risks of graft rejection and graft-versus-host disease (GVHD). With modern conditioning regimens and prophylaxis, outcomes have improved, and recent reports show encouraging results. Here, we present the first case from Northern India of a child with GT successfully treated with haploidentical HSCT [Table 1].

CASE REPORT

A 15-year-old boy, the second child of non-consanguineous parents, had recurrent mucocutaneous bleeding since infancy, requiring multiple transfusions. Prior to transplant, the patient was supported with and intermittent single donor platelet transfusions. Despite supportive care, he became refractory to platelet transfusions. Anti-HLA antibody screening was negative, excluding alloimmunisation. Baseline investigations confirmed type I GT with absent platelet aggregation with ADP, collagen, and epinephrine, but preserved ristocetin response. Genetic testing could not be performed as DNA analysis was not available in our centre and external testing was not affordable for the family. His brother, aged 18 years, was a haploidentical 5/10 HLA match and served as donor. The donor had normal platelet function with preserved aggregation responses on screening. Conditioning was fludarabine, busulfan, and cyclophosphamide; GVHD prophylaxis included tacrolimus and mycophenolate mofetil. Peripheral blood stem cells (CD34+ dose 1×107/kg) were infused on day 0. Neutrophils engrafted by day 14, platelets by day 18, and day 30 chimerism showed 99.4% donor cells. During conditioning and the preengraftment period, packed red cell and platelet transfusions were required for severe anemia, thrombocytopenia, and nasal bleeding related to myeloablation. Complications included grade 3 mucositis and mild cutaneous GVHD, both managed conservatively. At 7 months, he remains well and transfusion-independent, with 12.8 g/dL, 6.5×10/µL, platelets 150×10/µL [Figures 1 and 2].

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Figure 1:

Petechiae and ecchymoses over the trunk and hand.

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Figure 2:

Diffuse pigmentation and scarring over the face and upper limb in Glanzmann’s thrombasthenia.

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DISCUSSION

HSCT is the only curative therapy for GT. Most successful cases have used matched sibling donors, but many children lack suitable matches. Haploidentical HSCT expands donor availability and, with modern conditioning and GVHD prophylaxis, outcomes are improving. Our patient engrafted promptly with stable donor chimerism and manageable toxicities. This outcome is consistent with reports from Connor et al., ^[3] McColl and Gibson,^[4] and Flood et al., ^[5] who described durable remission after HSCT in GT. The case also underscores practical challenges in India, where donor registries are limited and transfusion refractoriness is common. Supportive care, including mucositis management and conservative GVHD treatment, contributed to success. Although follow-up is short, this case adds to growing evidence that haploidentical HSCT is feasible for GT where matched donors are lacking.

CONCLUSION

Haploidentical HSCT can achieve durable engraftment and restore transfusion independence in GT. In countries with limited registry access, it represents a practical, curative option.