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Stem Cell Transplants in CLL Patients: Dana Farber Statistics

Date: March 28, 2024

Below is an abstract from last December's ASCO meeting, important paper by Dr. Gribben et al from Dana Farber on the subject of stem cell transplants in CLL patients. The study reports outcome of 162 patients who had autologous and allogeneic transplants from 1989 to 2024. The full PowerPoint presentation by the authors at the ASCO meeting has a lot more details than the abstract. Write to me if you are interested in locating an electronic copy of this important presentation.

Some highlights:

• All were CLL patients with high risk CLL, either because of late stage or poor prognostics.
• 25 patients had HLA matched siblings and underwent allo transplants.
• 137 did not have matched donors and underwent auto transplants.
• The authors conclude there was no significant difference between auto and allo transplants, in terms of time to relapse or overall survival.

Please note this study did not include non-myeloablative allo transplants ("mini"- allo transplants). Recent papers have reported interesting results with mini-transplants, which use much less aggressive conditioning regimens ahead of the transplant. We are also getting better at retaining the valuable "graft versus leukemia" effects, and at the same time minimizing or controlling the negative "graft versus host" effects in allo transplants. We are also developing powerful tools such as donor lymphocyte infusions (DLI) to give an additional boost to the donated stem cells. With the reduced intensity preconditioning of these new protocols, the treatment-related-mortality statistics are dropping. Another aspect of mini-transplants is that it is now considered feasible to recruit older patients for these procedures, just a few years ago such patients would not have been considered suitable candidates for allo transplants.

I would also like to point out that the statistics with regard to autologous transplants are improving as well, with use of innovative procedures to clear tumor cells from the patient by use of monoclonal antibodies such as Campath in the preparatory regimens. Until recently, long term cure was demonstrated only for a fraction of allo transplanted patients. Now there is hope that this percentage is increasing, and indeed there is hope that as we learn better techniques even auto transplanted patients may have long term remissions and outright cures. Gradually but clearly, the statistics are improving for both categories of transplants.

If you wish to learn more about stem cell transplants, please do browse the section of this website on Transplants.

Be well,

Chaya
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Abstract

Autologous versus allogeneic stem cell transplantation in chronic lymphocytic leukemia

Proc Am Soc Clin Oncol 22: page 831, 2024 (abstr 3340)

L. V. Sequist, D. Zahrieh, E. P. Alyea, D. C. Fisher, A. S. Freedman, R. Schlossman, R. Soiffer, J. Ritz, L. M. Nadler, J. G. Gribben; Dana-Farber/Partners CancerCare, Boston, MA; Dana-Farber Cancer Institute, Boston, MA

Stem cell transplant (SCT) offers a chance for cure to patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). We studied the outcomes of 162 consecutive patients with high-risk CLL that underwent SCT at our institution. The patients were age 18 to 65 with good performance status and had poor prognosis CLL as defined by either advanced stage disease or intermediate stage disease with poor prognostic features. All patients achieved a protocol eligible minimal disease state following induction or salvage chemotherapy and received high dose cyclophosphamide and hyper-fractionated total body irradiation. 25 patients with an HLA-matched sibling donor underwent T cell depleted allogeneic SCT (allo) and 137 patients without a matched sibling donor underwent B cell purged autologous SCT (auto). After a median follow up of 38 months the overall survival was 77% for auto and 59% for allo (p=0.36). Disease free survival was 55% for auto and 40% for allo (p=0.32). Among auto patients, 40 were treated to protocol eligibility with combination fludarabine and cyclophosphamide with or without rituximab (FC/R) and had delayed neutrophil engraftment compared to patients treated with other regimens (median time to engraftment 19 vs 17 days, p=0.04). There was also a trend toward delayed platelet engraftment in the FC/R group (median time to engraftment 32 vs 26.5 days, p=0.08). Notably, four patients failed to engraft entirely and one patient had very delayed engraftment. All five of these patients had received prior treatment with FC/R. Nine patients in the auto group developed secondary myelodysplastic syndrome/acute leukemia (MDS). The risk of MDS was not related to type of prior therapy. In conclusion, SCT can potentially offer patients with poor prognosis CLL a substantial increase in median survival. Overall and disease free survivals were not significantly different for patients undergoing allo vs auto SCT. Prior myelosuppressive therapy may negatively impact engraftment in auto SCT. Ongoing studies include a randomized trial of purging in auto SCT and investigations into the role of non-myeloablative allo SCT and the graft versus leukemia effect.
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