We describe a 20-year-old Japanese woman with anaplastic large cell lymphoma in whom primary tracheal involvement was associated with life-threatening airway obstruction. After debulking surgery, the patient was successfully treated with chemotherapy and radiotherapy. A total of 28 cases of primary tracheal lymphoma were reviewed. Common clinical features included predominance of localized disease, respiratory symptoms resembling acute asthma, absence of hemoptysis, and rapid progression of tracheal stenosis. Various histological subtypes of primary tracheal lymphoma exist and are likely to determine prognosis.

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Late graft failure (LGF) without evidence of residual recipient cells is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-SCT) and often requires stem cell infusion from the same donor when the patient fails to respond to conventional therapies. We screened the peripheral blood (PB) of 14 patients who developed donor-type LGF at 2 to 132 months after allo-SCT for the presence of the markers for immune-mediated bone marrow (BM) failure. Increased glycosylphosphatidyl inositol-anchored protein-deficient (GPI-AP) leukocytes, which accounted for .009% to 0.147% of the total granulocytes, were detected in 5 patients (severe aplastic anemia, n = 2; follicular lymphoma, n = 1; acute lymphoblastic leukemia, n = 1; myelodysplastic syndromes; n = 1) and 4.7% to 81.2% HLA-allele-lacking leukocytes (HLA-LLs) were detected in 2 patients (acute myelogenous leukemia, n = 1; and myelodysplastic syndromes, n = 1). Three of the 5 patients with increased GPI-AP leukocytes were treated with antithymocyte globulin (ATG), and 2 patients achieved transfusion independence. These results suggest that immune mechanisms that are similar to acquired aplastic anemia underlie condition of approximately one-half of the patients with donor-type LGF, and that in patients with increased GPI-AP cells, donor-derived hematopoiesis may be restored by ATG therapy alone without donor stem cell infusion.

Aberrantly expressed self-antigens in leukemic cells serve as leukemia-associated-antigens (LAAs) of leukemia reactive T cells. Although such self-antigen-derived LAAs potentially induce high avidity CTLs in patients with leukemia, these CTLs usually do not persist due to apoptosis upon encountering leukemic cells. In allogeneic stem cell transplant (allo-SCT) recipients with leukemia, residual leukemic cell may sensitize donor-derived T cells by LAA in vivo and induce high avidity CTLs specific to leukemic cells. Cyclin-dependent kinase 2 (CDK2) is a cell cycle regulator protein that is aberrantly expressed in AML, MDS, ALL and MCL cells. We previously reported that CDK2-derived nonamer peptides (CDK2158: TYTHEVVTL, CDK2167: WYRQPEILL, CDK2178: KYYSTAVDI) avidly bound to HLA-A24 molecule to elicit each peptide-specific CTL from peripheral blood mononuclear cells (PBMCs) of healthy individuals (Blood. 106 (11): a3103. 2005). When we generated CDK2158-specific CD8+ T cells from an HLA identical sibling donor of a patient with AML by stimulating donor PBMCs with CDK2158-coated HLA-A24-transfected T2, CDK2158-specific CD8+ T cells preferentially killed the recipient AML cells which aberrantly expressed CDK2 proteins. The percentages of specific lysis in the 51Cr-release assay at an E/T ratio of 40 were 36.8% for AML cells and 24.8% for autologous PBMCs. To determine if CDK2-specific CD8+ T cells are present in PBMCs from allo-SCT patients, we studied 14 patients possessing HLA-A24 [6 patients with AML (2 AML-M0, 3 AML-M2, 1 AML with multilinage dysplasia), 1 with MDS, 1 with CML, 2 with ALL, 2 with MCL and 2 with RCC] using CDK2158/A24 and CDK2178/A24 multimers. Cryopreserved PBMCs obtained before and 4–73 months after allo-SCT were assayed for multimer staining. The source of graft was unrelated BM in 4, related BM in 2, related PBMC in 3 and CB in 5 patients. All CB and 1 BM graft were HLA mismatched. Seven patients were in complete remission (CR) at the time of SCT while 7 were in non-CR. Ten patients remained in CR 4–79 months after SCT. Small populations (0.13–0.77 % of lymphocyte) of CDK2158 and CDK2178-specific CTL were detectable in 5 patients (3 with AML-M2, 1 with CML and 1 with ALL) 10–73 months after SCT. All of the 5 remained in CR 11–79 months after SCT. Only one of them had active cGvHD at sampling. On the other hand, among 7 patients who did not show an increase in the proportion of neither CDK2158 nor CDK2178-specific CTLs, 2 patients with AML-M0 relapsed 4 and 5 months after SCT, respectively. Both of them had active cGvHD at sampling. CDK2-specific CTLs were also undetectable in 2 patients with RCC after allo-SCT. These data provide evidence for the first time that CDK2-specific CTLs can be induced from donor-derived T cells without peptide immunization possibly due to in vivo sentitization of donor T cells by residual leukemic cells. Vaccination with CDK2-derived peptides after allo-SCT may therefore be useful in inducing CDK2-specific CTLs and thereby preventing relapse of leukemia. Fig. Appearance of CDK2-CTLs after allo SCT in patients with leukemia in remission. Fig. Appearance of CDK2-CTLs after allo SCT in patients with leukemia in remission.