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Pre-transplant myeloid and immune suppression, upfront plerixafor mobilization and post-transplant cyclophosphamide: novel strategy for haploidentical transplant in sickle cell disease

Bone Marrow Transplantation volume 56, pages 492–504 (2021)Cite this article

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Abstract

Allogenic hematopoietic stem cell transplant is the only curative option for symptomatic sickle cell disease (SCD). HLA haploidentical related donor transplants are associated with high graft failure rates. We conceptualized a novel protocol (APOLLO protocol) using pre-transplant immune and myelosuppression (PTIS) using fludarabine, cyclophosphamide, and dexamethasone followed by augmented John Hopkins protocol by adding thiotepa to conditioning. Twenty-five consecutive patients suffering from symptomatic SCD were enrolled into the study. We added upfront plerixafor to granulocyte colony stimulating factor (GCSF) for mobilization of healthy donors. Graft versus host disease (GvHD) prophylaxis was done using post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil. Graft failure was not seen in any of our patients. Five patients developed acute grade II/IV GvHD (4 classical acute, 1 late onset), 3 had limited chronic GvHD. Out of 25 evaluable patients, 22 are alive and disease free, making an overall survival (OS) and disease-free survival (DFS) of 88% with a median follow up of 485 days (range 198–802). T-cell-replete haploidentical transplant with PTIS, augmented John Hopkins conditioning and plerixafor based mobilization is a safe and effective way of treating patients suffering from SCD with minimal or no risk of graft failure and acceptable GvHD rates.

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Fig. 1: Treatment schema APOLLO protocol.
Fig. 2: Neutrophil engraftment of patients treated on APOLLO protocol.
Fig. 3: Platelet engraftmnet of patients treated on APOLLO protocol.
Fig. 4: Probability of overall survival and event free survival of patients treated on APOLLO protocol.
Fig. 5: Time to Graft versus Host Disease Acute and Chronic.

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Acknowledgements

We would like to acknowledge Ms Manju Joseph and the entire nursing team for the excellent execution of the protocol and state of art clinical care given to the patients, to Ms Himshikha Yadav who fulfilled the job of BMT coordinator to best of her capacity. Ms Bharti Sharma, Senior data analyst helped in maintenance and compilation of the entire data and also in statistical analysis.

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  1. Center for Bone Marrow Transplant and Cellular Therapy, Indraprastha Apollo Hospital, New Delhi, India

    Gaurav Kharya, Atish Bakane, Shirali Agarwal & Archana Rauthan

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  1. Gaurav Kharya
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  2. Atish Bakane
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GK conceptualized the protocol and drafted the paper. SA, AB, AR compiled the data and did the statistical analysis. All the authors contributed, read and approved the final version of the manuscript.

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Correspondence to Gaurav Kharya.

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Center for Bone Marrow Transplant and Cellular Therapy, Indraprastha Apollo Hospital, New Delhi, India.

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Kharya, G., Bakane, A., Agarwal, S. et al. Pre-transplant myeloid and immune suppression, upfront plerixafor mobilization and post-transplant cyclophosphamide: novel strategy for haploidentical transplant in sickle cell disease. Bone Marrow Transplant 56, 492–504 (2021). https://doi.org/10.1038/s41409-020-01054-3

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