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Chimerism does not predict for outcome after alemtuzumab based conditioning

Bone Marrow Transplantation volume 40, page 181 (2007)Cite this article

We and others have studied the combination of fludarabine, melphalan and alemtuzumab as conditioning regimen for allogeneic transplantation and have observed a very low incidence of acute and chronic GVHD and excellent tolerability.1, 2 We have reported previously that in patients with myeloid malignancies receiving this conditioning regimen, post-transplant expression of WT1 does not predict for disease recurrence.3 Here, we present results of day 30 and day 100 chimerism in 94 consecutive patients – conditioned with fludarabine, melphalan and alemtuzumab – who survived at least 1 month after transplant. All patients had hematologic malignancies and underwent related or unrelated donor transplant. All patients received fludarabine (30 mg/m2/day) i.v.) and alemtuzumab (20 mg/day) i.v. for 5 consecutive days, followed by a single dose of melphalan (140 mg/m2). Post-transplant immunosuppression was achieved with tacrolimus initially administered i.v. beginning day −2 and then orally from engraftment until day 100. At day 100, tacrolimus was tapered over a period of 2–3 weeks, unless there was evidence of acute or chronic GVHD. Early withdrawal of immunosuppression was used if disease relapse occurred. Engraftment occurred in 91 of the 94 patients. After an average follow-up of 24 months (range 1–40 months), a relapse occurred in 39/94 (42%) of patients and 47/94 (50%) have died. Twenty-two developed grade II–IV acute GVHD and 15 developed chronic GVHD.

Bone marrow and/or peripheral blood samples were obtained at approximately 30 and 100 days following stem cell infusion using a PCR-based variable number of tandem repeats (VNTR) analysis. This method has a sensitivity of approximately 5%. All analysis were performed on unfractionated bone marrow or blood samples. Samples were obtained from 86 patients on day 30 (72 bone marrow, 14 peripheral blood) and from 66 of 81 (57 bone marrow, 9 peripheral blood) evaluable patients (81%) on day 100. The mean rate of donor chimerism on day 30 was 93% donor (95% confidence interval (CI): 90–97%). Only one patient had less than 60% donor chimerism on day 30. The mean chimerism on day 100 was 88% (95% CI: 83–92%). Nine patients had less than 80% chimerism on day 100. In five of these, the low chimerism was indicative of near simultaneous relapse, but four had more prolonged remissions. We did not find any correlation between rates of chimerism on day 30 or day 100 and outcomes including progression-free survival, overall survival and acute or chronic GVHD. Also, the trend in chimerism between day 30 and day 100 did not correlate with any of the above outcomes.

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References

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Authors and Affiliations

  1. Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA

    L Michaelis, A S Artz, J Kline, D Pollyea, W Stock, E Rich, D Collins-Jones, B Casey, P Del Cerro & K van Besien

  2. Deparment of Health Studies, The University of Chicago, Chicago, IL, USA

    S Lin

  3. Department of Pathology, The University of Chicago, Chicago, IL, USA

    L Joseph

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  1. L Michaelis
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  2. S Lin
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  3. L Joseph
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  4. A S Artz
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  5. J Kline
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  6. D Pollyea
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  7. W Stock
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  8. E Rich
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  9. D Collins-Jones
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  11. P Del Cerro
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  12. K van Besien
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Correspondence to K van Besien.

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Michaelis, L., Lin, S., Joseph, L. et al. Chimerism does not predict for outcome after alemtuzumab based conditioning. Bone Marrow Transplant 40, 181 (2007). https://doi.org/10.1038/sj.bmt.1705707

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