Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk.

Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), which is a subtype of non-Hodgkin lymphoma, are relatively uncommon lymphoproliferative types of cancer. These malignancies are highly curable with initial treatment. Nonetheless, some patients are refractory to or relapse after first- and second-line therapies, and outcomes for these patients are less promising. Brentuximab vedotin is a CD30-directed antibody-cytotoxic drug conjugate that has demonstrated efficacy in response rates (objective response rates and complete response) when given to patients with refractory or relapsed HL and sALCL. Although not compared directly in clinical trials, the response rates with brentuximab vedotin are higher than those of several current treatments for refractory or relapsed HL and sALCL. Adverse effects associated with brentuximab vedotin are considered manageable. Nonetheless, several serious adverse effects (e.g., neutropenia, peripheral sensory neuropathy, tumor lysis syndrome, Stevens-Johnson syndrome, and progressive multifocal leukoencephalopathy, resulting in death) have been reported with its use. Despite a lack of survival and patient reported outcome data, the United States Food and Drug Administration (FDA) granted accelerated approval to brentuximab vedotin for the treatment of HL after failure of autologous stem cell transplantation or at least two combination chemotherapy regimens, and for sALCL after failure of at least one combination chemotherapy regimen. With this approval, brentuximab vedotin is the first FDA-approved agent for the treatment of HL in over three decades and the first agent specifically indicated to treat sALCL. Results of ongoing prospective trials should determine if brentuximab vedotin has a survival benefit when compared directly with standard treatment and if brentuximab vedotin is safe and efficacious when given earlier in the disease process, or when used with other chemotherapy for the treatment of HL and sALCL or other CD30-positive malignancies.

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