Catherine S Perry

Interests

Teaching

Pathophysiology of leukemia and lymphomaImmunobiology of transplantation

Research

Diagnosis and prognostic factors in leukemia and lymphoma as assessed by morphology, flow cytometry, immunohistochemistry and cytogenetic/molecular findings. Using these factors in collaborative research.Immunobiology of transplantation, both pre- and post- transplant for solid organ and bone marrow recipients. How HLA type and antibody status affects transplant outcome

Courses

Scholarly Contributions

Journals/Publications

• Harris, D. T., Badowski, M., Jernigan, B., Sprissler, R., Edwards, T., Cohen, R., Paul, S., Merchant, N., Weinkauf, C. C., Bime, C., Erickson, H. E., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., Campion, J., , Chopra, M., et al. (2021). SARS-CoV-2 Rapid Antigen Testing of Symptomatic and Asymptomatic Individuals on the University of Arizona Campus. Biomedicines, 9(5).
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  SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.
• Otsuji, J., Girard, N., Perry, C. S., Fuchs, D., & Lai, L. (2020). Sibling Donor-Derived Myeloid Sarcoma After Hematopoietic Stem Cell Transplant. Human Pathology.
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  Janelle Otsuji, MD (jjotsuji@pathology.arizona.edu); Nicole Girard, MD; Catherine Spier, MD; Deborah Fuchs, MD; Li-Wen Lai, PhD. Department of Pathology, The University of Arizona, Tucson, Arizona.Myeloid sarcoma (MS) occurs in 8% to 20% of post–allogeneic hematopoietic stem cell transplant (allo-HSCT) patients, mostly from recipient's relapsed leukemia. Donor-derived MS (DDMS) is extremely rare. We report 2 cases of DDMS after successful allo-HSCT from human leukocyte antigen (HLA)-identical, sex-mismatched siblings. Donor origin was confirmed by both cytogenetic and molecular chimerism tests. Case 1 was a 50-year-old man with history of KMT2A-rearranged acute myeloid leukemia (AML) presented with bilateral knee soft tissue masses 5 years post–allo-HSCT. Knee biopsy revealed infiltrative large cells with blastic morphology expressing CD4, CD10, CD38, CD33 (dim), subset MPO, while negative for CD117 and CD34 (Table). Interphase fluorescence in situ hybridization (FISH) analysis showed gain of chromosomes 5/6/8/15q/20q/21q and loss of 17q/20q with 95.5% cells showing donor origin. Concurrent bone marrow biopsies showed donor-derived karyotype//46,XX,del(20)(q11.2q13.3)[4]/46,XX[16] versus 46,XY,t(6;11)(q27;q23)[18]/46,XY[2] at diagnosis 8 years prior (Table). Case 2 was a 40-year-old man with history of AML with myelodysplasia-related changes (AML-MRC) presented with a testicular mass 5 years post-HSCT. Orchiectomy yielded a mass of 163 g and 8.7 cm in diameter. Microscopically, there was diffuse effacement of the testis architecture with large cells demonstrating an immature myeloid phenotype CD34+, CD117+, MPO dim subset, and aberrant CD7. FISH analysis showed 100% of cells showing XX donor cells. Concurrent bone marrow biopsies showed 100% normal XX donor cells. Both cases developed DDMS 5 years after allo-HSCT from siblings. Verifying donor origininAML relapseiscriticalas transformed donor cells may have different genetic alterations and behaviors from initial AML. Our case 2 is likely the first testicular sibling-DDMS in the literature.
• Otsuji, J., Girard, N., Perry, C. S., Fuchs, D., & Lai, L. (2021). Sibling Donor-Derived Myeloid Sarcoma After Hematopoietic Stem Cell Transplant. Human Pathology, 24. doi:https://doi.org/10.1016/j.ehpc.2021.200512
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  Janelle Otsuji, MD (jjotsuji@pathology.arizona.edu); Nicole Girard, MD; Catherine Spier, MD; Deborah Fuchs, MD; Li-Wen Lai, PhD. Department of Pathology, The University of Arizona, Tucson, Arizona. Myeloid sarcoma (MS) occurs in 8% to 20% of post–allogeneic hematopoietic stem cell transplant (allo-HSCT) patients, mostly from recipient's relapsed leukemia. Donor-derived MS (DDMS) is extremely rare. We report 2 cases of DDMS after successful allo-HSCT from human leukocyte antigen (HLA)-identical, sex-mismatched siblings. Donor origin was confirmed by both cytogenetic and molecular chimerism tests. Case 1 was a 50-year-old man with history of KMT2A-rearranged acute myeloid leukemia (AML) presented with bilateral knee soft tissue masses 5 years post–allo-HSCT. Knee biopsy revealed infiltrative large cells with blastic morphology expressing CD4, CD10, CD38, CD33 (dim), subset MPO, while negative for CD117 and CD34 (Table). Interphase fluorescence in situ hybridization (FISH) analysis showed gain of chromosomes 5/6/8/15q/20q/21q and loss of 17q/20q with 95.5% cells showing donor origin. Concurrent bone marrow biopsies showed donor-derived karyotype//46,XX,del(20)(q11.2q13.3)[4]/46,XX[16] versus 46,XY,t(6;11)(q27;q23)[18]/46,XY[2] at diagnosis 8 years prior (Table). Case 2 was a 40-year-old man with history of AML with myelodysplasia-related changes (AML-MRC) presented with a testicular mass 5 years post-HSCT. Orchiectomy yielded a mass of 163 g and 8.7 cm in diameter. Microscopically, there was diffuse effacement of the testis architecture with large cells demonstrating an immature myeloid phenotype CD34+, CD117+, MPO dim subset, and aberrant CD7. FISH analysis showed 100% of cells showing XX donor cells. Concurrent bone marrow biopsies showed 100% normal XX donor cells. Both cases developed DDMS 5 years after allo-HSCT from siblings. Verifying donor origininAML relapseiscriticalas transformed donor cells may have different genetic alterations and behaviors from initial AML. Our case 2 is likely the first testicular sibling-DDMS in the literature.
• Perry, C. S. (2018). Co-targeting Aurora kinase with PD-L1 and PI3K abrogates immune checkpoint mediated proliferation in Peripheral B-cell Lymphoma: A novel theraeutic strategy.. Oncotarget.
• Spier, C. M. (2016). Continued excellent outcomes in previously untreated follicular lymphoma patients after treatment with CHOP plus rituximab or CHOP plus (131) iodine-tositumomab- long term follow-up of phase III randomezed study SWOG S0016. American Society of Hematology Annual Meeting.
• Spier, C. M. (2016). Prolifereation associated immune suppression co-targeted with Alisertib plus anti-PD-1 and/or PI3K inhibition in peripheral T-cell lymphoma. Leukemia.
• Bixby, B., Cristan, E., Aini, T. E., Sam, A., Capaldi, A. P., Perry, C. S., Scott, S. J., Bhattacharya, D., Nikolich-Žugich, J., Sprissler, R., LaFleur, B., Harris, D. T., Mosier, J., Hypes, C., Kaplan, M. E., Edwards, T., Dake, M. D., Knepler, J., Insel, M., , Chopra, M., et al. (2020). Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure. Cold Spring Harbor Laboratory - medRxiv. doi:10.1101/2020.08.14.20174490
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  We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
• Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., Aini, T. E., Rischard, F., , Campion, J., et al. (2020). Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure. medRxiv : the preprint server for health sciences.
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  We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
• Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., , Campion, J., et al. (2020). Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity, 53(5), 925-933.e4.
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  We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.
• Perry, C. S. (2018). Continued Excellent Outcomes in Previously Untreated Follicular Lymphoam Patients after Treatment with CHOP Plus Rituximab or CHOP Plus 131Iodine-Tositumomab: Long Term Follow-up of Phase III Randomized Study SWOG-S0016. Journal of Clinical Oncology.
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  Follicular lymphomas have excellent outcome with either of 2 treatment options
• Perry, C. S. (2018). Impact of histological grading on survival in the SWOG S0016 follicular lymphoma cohort. haematologica, 103, e151.
• Perry, C. S. (2018). Phase I Study of the Investigational Aurora A Kinase Inhibitro Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma.. Clin Cancer Res, 24(24), 6150-6159. doi:10.1158.1078-0432.CCR-18-0286
• Perry, C. S. (2018). Subclonal mutations of TP53 are common in untreated follicular lymphoma and mutation status is predictive of PFS when CHOP is combined with 131-Iodine Tositumomab but not with Rituximab: An analysis of SWOG S0016. Blood, 132(Suppl 1), 919. doi:https://doi.org/10.1182/blood-2018-99-111399
• Rimsza, L. M., Li, H., Braziel, R. M., Spier, C. M., Persky, D. O., Dunlap, J., LeBlanc, M., Bartlett, N., Leonard, J. P., Smith, S. M., Press, O. W., & Friedberg, J. W. (2018). Impact of histological grading on survival in the SWOG S0016 follicular lymphoma cohort. Haematologica, 103(4), e151-e153.
• Shadman, M., Li, H., Rimsza, L., Leonard, J. P., Kaminski, M. S., Braziel, R. M., Spier, C. M., Gopal, A. K., Maloney, D. G., Cheson, B. D., Dakhil, S., LeBlanc, M., Smith, S. M., Fisher, R. I., Friedberg, J. W., & Press, O. W. (2018). Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 36(7), 697-703.
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  Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133-tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.
• Perry, C. S. (2017). Co-targeting Aurora kinase with PD-L1 and PI3K abrogates immune checkpoint mediated proliferation in Peripheral B-cell Lymphoma: A novel theraeutic strategy.. Oncotarget, 8(59), 1003260100338.
• Perry, C. S. (2017). Inhibition of polyploidy and senescence induces intrinsic apoptosis in double hit or double expresser DLBCL. Cancer Res, 77(13 Suppl), 4057. doi:10.1158/1538-7445.AM2017-4057
• Spier, C. M. (2017). Disruption of aneuploidy and senescence induced by Aurora inhibition promotes intrinsic apoptosis in double hit or double expresser diffuse large B-cell lymphomas. Mol Cancer Ther, 16(10), 2083-2093. doi:10.1158/1535-7163.MCT-17-0089
• Barr, P. M., Li, H., Spier, C., Mahadevan, D., LeBlanc, M., Ul Haq, M., Huber, B. D., Flowers, C. R., Wagner-Johnston, N. D., Horwitz, S. M., Fisher, R. I., Cheson, B. D., Smith, S. M., Kahl, B. S., Bartlett, N. L., & Friedberg, J. W. (2015). Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 33(21), 2399-404.
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  Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL).
• Persky, D. O., Miller, T. P., Unger, J. M., Spier, C. M., Puvvada, S., Stea, B. D., Press, O. W., Constine, L. S., Barton, K. P., Friedberg, J. W., LeBlanc, M., & Fisher, R. I. (2015). Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood, 125(2), 236-41.
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  In the S0313 trial, we evaluated the impact of adding ibritumomab tiuxetan consolidation to 3 cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy plus involved field radiotherapy (IFRT) in patients with limited-stage aggressive B-cell non-Hodgkin lymphoma (LD-NHL). Patients with at least 1 stage-modified adverse risk factor (nonbulky stage II, age >60 years, elevated lactate dehydrogenase, or World Health Organization performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40 to 50 Gy of IFRT. An ibritumomab tiuxetan regimen was initiated 3 to 6 weeks following IFRT. Forty-six patients were registered and eligible, with median follow-up of 7.3 years. The progression-free survival estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. The overall survival estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. Grade 4 adverse events occurring more than once included neutropenia (8), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. In conclusion, patients with high-risk LD-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. The clinical trial was registered at www.clinicaltrials.gov as #NCT00070018.
• Spier, C. M., Persky, D. O., Miller, T. P., Unger, J. M., Puvvada, S., Stea, D. B., Press, O. W., Constine, L. S., Barton, K. P., Friedberg, J. W., LeBlanc, M., & Fisher, R. I. (2015). Ibritumomab tiuxetan consolidation after 3 cycles of CHOP plus radiotherapy for high risk limited stage aggressive B-cell lymphoma. Blood, 125, 236-241.
• Barr, P. M., Miller, T. P., Friedberg, J. W., Peterson, D. R., Baran, A. M., Herr, M., Spier, C. M., Cui, H., Roe, D. J., Persky, D. O., Casulo, C., Littleton, J., Schwartz, M., Puvvada, S., Landowski, T. H., Rimsza, L. M., Dorr, R. T., Fisher, R. I., Bernstein, S. H., & Briehl, M. M. (2014). Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma. Blood, 124(8), 1259-65.
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  Lymphoma cells are subject to higher levels of oxidative stress compared with their normal counterparts and may be vulnerable to manipulations of the cellular redox balance. We therefore designed a phase 2 study of imexon (Amplimexon/NSC-714597), a prooxidant molecule, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Imexon was administered at 1000 mg/m(2) IV daily for 5 days in 21-day cycles. Gene expression analysis performed on pretreatment tumor specimens included 13 transcripts used to generate a redox signature score, previously demonstrated to correlate with lymphoma prognosis. Twenty-two patients were enrolled having follicular (n = 9), diffuse large B-cell (DLBCL) (n = 5), mantle cell (n = 3), transformed follicular (n = 2), small lymphocytic (n = 2), and Burkitt (n = 1) lymphoma. The most common grade 3/4 adverse events were anemia (14%) and neutropenia (9%). The overall response rate was 30%, including responses in follicular lymphoma (4 of 9) and DLBCL (2 of 5). Gene expression analyses revealed CD68 and the redox-related genes, GPX1 and SOD2, as well as a higher redox score to correlate with clinical responses. Therefore, pretreatment markers of oxidative stress may identify patients likely to respond to this therapeutic approach. This trial was registered at www.clinicaltrials.gov as #NCT01314014.
• Gustafson, H. L., Yao, S., Goldman, B. H., Lee, K., Spier, C. M., LeBlanc, M. L., Rimsza, L. M., Cerhan, J. R., Habermann, T. M., Link, B. K., Maurer, M. J., Slager, S. L., Persky, D. O., Miller, T. P., Fisher, R. I., Ambrosone, C. B., & Briehl, M. M. (2014). Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma. American journal of hematology, 89(6), 639-45.
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  Variable survival outcomes are seen following treatment for aggressive non-Hodgkin lymphoma (NHL). This study examined whether outcomes for aggressive B-cell NHL are associated with single nucleotide polymorphisms (SNPs) in oxidative stress-related genes, which can alter drug metabolism and immune responses. Genotypes for 53 SNPs in 29 genes were determined for 337 patients given anthracycline-based therapies. Their associations with progression-free survival (PFS) and overall survival (OS) were estimated by Cox proportional hazard regression; associations with hematologic toxicity were estimated by logistic regression. To validate the findings, the top three SNPs were tested in an independent cohort of 572 DLBCL patients. The top SNPs associated with PFS in the discovery cohort were the rare homozygotes for MPO rs2243828 (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.14-3.06, P = 0.013), AKR1C3 rs10508293 (HR = 2.09, 95% CI = 1.28-3.41, P = 0.0032) and NCF4 rs1883112 (HR = 0.66, 95% CI = 0.43-1.02, P = 0.06). The association of the NCF4 SNP with PFS was replicated in the validation dataset (HR = 0.66, 95% CI = 0.44-1.01, P = 0.05) and the meta-analysis was significant (HR = 0.66, 95% CI = 0.49-0.89, P < 0.01). The association of the MPO SNP was attenuated in the validation dataset, while the meta-analysis remained significant (HR = 1.64, 95% CI = 1.12-2.41). These two SNPs showed similar trends with OS in the meta-analysis (for NCF4, HR = 0.72, 95% CI = 0.51-1.02, P = 0.07 and for MPO, HR = 2.06, 95% CI = 1.36-3.12, P < 0.01). In addition, patients with the rare homozygote of the NCF4 SNP had an increased risk of hematologic toxicity. We concluded that genetic variations in NCF4 may contribute to treatment outcomes for patients with aggressive NHL.
• Perry, C. S. (2014). Genetic polymophisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma. Am J Hematology, 89(6), 639-645.
• Spier, C. M. (2014). Assessment of carbonic anhydrase IX expression and extracellular pH in B-cell lymphoma cell line models. Leuk Lymphoma, 10, 1-8.
• Spier, C. M. (2014). Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory b-cell non-Hodgkin lymphoma. Blood, 124, 1259-1265.
• Mahadevan, D., Unger, J. M., Spier, C. M., Persky, D. O., Young, F., LeBlanc, M., Fisher, R. I., & Miller, T. P. (2013). Phase 2 trial of combined cisplatin, etoposide, gemcitabine, and methylprednisolone (PEGS) in peripheral T-cell non-Hodgkin lymphoma: Southwest Oncology Group Study S0350. Cancer, 119(2), 371-9.
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  Patients with peripheral T-cell lymphomas (PTCLs) have inferior progression-free survival (PFS) and overall survival (OS) compared with patients who have aggressive B-cell non-Hodgkin lymphoma. Because PTCLs over express multidrug resistance gene 1/P-glycoprotein (MDR-1/P-gp), we devised platinum, etoposide, gemcitabine, and methylprednisolone (PEGS) with agents that are not substrates of the efflux pump. Gemcitabine was included because of its excellent single-agent activity in PTCL.
• Persky, D. O., Unger, J. M., Spier, C. M., Stea, B., LeBlanc, M., McCarty, M. J., Rimsza, L. M., Fisher, R. I., Miller, T. P., & , S. O. (2008). Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 26(14), 2258-63.
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  To evaluate the effect of rituximab in limited-stage diffuse large B-cell lymphoma (DLBCL), we conducted a multicenter phase II trial combining rituximab with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP) followed by involved-field radiation therapy (IFRT).
• Miller, T. P., Spier, C. M., & Rimsza, L. (2006). Diffuse aggressive histologies of non-hodgkin lymphoma: treatment and biology of limited disease. Seminars in hematology, 43(4), 207-12.
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  A quarter century has passed since the paradigm for treating aggressive histologies of non-Hodgkin lymphoma (NHL) presenting with limited extent of disease (LD) changed from using aggressive surgical staging techniques followed by primary radiotherapy (RT) to clinical staging followed by initial treatment with doxorubicin-containing chemotherapy (CT). This paradigm shift occurred for two reasons. First, unlike the predictable contiguous spread of Hodgkin lymphoma from one lymph node region to the next, the NHLs are largely systemic diseases characterized by early hematogenous spread. Second, the discovery of a potential curative combination of drugs, including cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), for use in advanced disease could eradicate micro-metastatic disease in patients with LD. The focus of current investigation on controlling the systemic nature of the disease has not changed. In this regard, new effective systemic therapies using combination chemotherapy plus monoclonal antibodies have resulted in improved outcome for patients with advanced disease and those treatment strategies are now under investigation in patients with LD.
• Rimsza, L. M., Roberts, R. A., Miller, T. P., Unger, J. M., LeBlanc, M., Braziel, R. M., Weisenberger, D. D., Chan, W. C., Muller-Hermelink, H. K., Jaffe, E. S., Gascoyne, R. D., Campo, E., Fuchs, D. A., Spier, C. M., Fisher, R. I., Delabie, J., Rosenwald, A., Staudt, L. M., & Grogan, T. M. (2004). Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood, 103(11), 4251-8.
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  The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better survival. We further analyzed the effects of HLA-DRA on survival and correlated gene expression with protein status and tumor-infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10% of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group, and 55% for patients in the highest 50%. Further analysis demonstrated that the hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment for the International Prognostic Index did not alter the impact of HLA-DRA on survival. Other MHC class II genes were found to predict survival similarly. Microarray HLA-DRA expression correlated with the presence or absence of human leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor-infiltrating CD8(+) T cells were detected in MHC class II-negative cases compared with positive cases (2.8% versus 11.0%; P =.001), supporting the hypothesis that loss of tumor immunosurveillance has a devastating effect on patient outcome in DLBCL.
• Al-Uzri, A. Y., Seltz, B., Yorgin, P. D., Spier, C. M., & Andreoni, K. (2002). Successful renal transplant outcome after intravenous gamma-globulin treatment of a highly sensitized pediatric recipient. Pediatric transplantation, 6(2), 161-5.
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  Approximately 10% of patients on the renal transplant (Tx) cadaver waiting list have high (> 20%) panel-reactive antibody (PRA) levels to human leukocyte antigens (HLA). Intravenous gamma-globulin (IVIG) has been shown to reduce anti-HLA cytotoxic antibody levels through an anti-idiotypic antibody-blocking effect. We report a successful renal Tx outcome in a 7-yr-old-girl with high PRA levels owing to a failed renal Tx who experienced a significant reduction in PRA levels (from 96% to 0%) concomitant with IVIG therapy. IVIG was infused weekly (500 mg/kg/week) for 3 consecutive weeks every 12 weeks. Thirty-four months after starting IVIG therapy, the PRA activity dropped to zero and IVIG was stopped. Then IVIG therapy was resumed after 8 months due to a rebound in PRA activity to 52%. Forty-four months after starting IVIG therapy, the patient was cross-matched with a cadaver donor who shared three antigens with the first living donor. The cross-match was positive with the recipient's sera obtained prior to IVIG therapy and negative with the recipient's sera obtained post-IVIG therapy. A successful cadaver renal Tx was performed using anti-thymocyte globulin (ATGAM) induction therapy and a tacrolimus-based immunosuppression protocol. IVIG was given (1 g/kg) prior to Tx and at day 4 post-operatively. A single mild acute rejection episode occurred 10 days post-transplantation that responded to pulse methylprednisolone therapy and an increase in the tacrolimus oral dose. We conclude that a prolonged course of IVIG infusions, without immunosuppressive medications or plasmapheresis, is likely to have been beneficial in modulating the immune response in this highly sensitized recipient. Randomized multicenter trials are required to define the role of IVIG in this specific population.

Presentations

• Reveles, C., Perry, C. S., Fuchs, D., Heimbigner, A., & Hansen Smith, M. (2023, November). From Sarcoidosis to Lymphoma: A Diagnostic Journey to Peripheral T Cell Lymphoma, NOS
  
  Presentation by Mary Hansen Smith, MD. Progress in T- and NK-Cell Lymphomas/LeukemiasSociety for Hematopathology.

Poster Presentations

• Lai, L., Fuchs, D., Perry, C. S., Girard, N., & Otsuji, J. (2020, October/2020). Sibling Donor-Derived Myeloid Sarcoma After Hematopoietic Stem Cell Transplant. CAP20 annual meeting. virtual meeting: College of American Pathologists.
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  Janelle Otsuji, MD (jjotsuji@pathology.arizona.edu); Nicole Girard, MD; Catherine Spier, MD; Deborah Fuchs, MD; Li-Wen Lai, PhD. Department of Pathology, The University of Arizona, Tucson, Arizona.Myeloid sarcoma (MS) occurs in 8% to 20% of post–allogeneic hematopoietic stem cell transplant (allo-HSCT) patients, mostly from recipient's relapsed leukemia. Donor-derived MS (DDMS) is extremely rare. We report 2 cases of DDMS after successful allo-HSCT from human leukocyte antigen (HLA)-identical, sex-mismatched siblings. Donor origin was confirmed by both cytogenetic and molecular chimerism tests. Case 1 was a 50-year-old man with history of KMT2A-rearranged acute myeloid leukemia (AML) presented with bilateral knee soft tissue masses 5 years post–allo-HSCT. Knee biopsy revealed infiltrative large cells with blastic morphology expressing CD4, CD10, CD38, CD33 (dim), subset MPO, while negative for CD117 and CD34 (Table). Interphase fluorescence in situ hybridization (FISH) analysis showed gain of chromosomes 5/6/8/15q/20q/21q and loss of 17q/20q with 95.5% cells showing donor origin. Concurrent bone marrow biopsies showed donor-derived karyotype//46,XX,del(20)(q11.2q13.3)[4]/46,XX[16] versus 46,XY,t(6;11)(q27;q23)[18]/46,XY[2] at diagnosis 8 years prior (Table). Case 2 was a 40-year-old man with history of AML with myelodysplasia-related changes (AML-MRC) presented with a testicular mass 5 years post-HSCT. Orchiectomy yielded a mass of 163 g and 8.7 cm in diameter. Microscopically, there was diffuse effacement of the testis architecture with large cells demonstrating an immature myeloid phenotype CD34+, CD117+, MPO dim subset, and aberrant CD7. FISH analysis showed 100% of cells showing XX donor cells. Concurrent bone marrow biopsies showed 100% normal XX donor cells. Both cases developed DDMS 5 years after allo-HSCT from siblings. Verifying donor origininAML relapseiscriticalas transformed donor cells may have different genetic alterations and behaviors from initial AML. Our case 2 is likely the first testicular sibling-DDMS in the literature.
• Perry, C. S., Burak, R., Li, H., Adlowitz, D. G., Spence, J. M., Leblanc, M. L., Rimsza, L. M., Braziel, R. M., Kaminski, M. S., Leonard, J. P., Fisher, R. I., Smith, S. M., & Friedberg, J. W. (2019, December). Intrclonal heterogeneity caused by activation-induced cytidine deaminase is not a prognostic biomarker in untreated advanced stage follicular lymphoma: an analysis of SWOG S0016. Annual American Society of Hematology Meeting. Orlando, Florida: American Society of Hematology.
• Perry, C. S. (2017, Fall). Inability to Report Platelet Counts Due to Interference of Automated Platelet Counting by Microschistocytes: A Caveat in Severely Ill Patients. Annual ASCP Meeting. Chicago, IL: Amercian Society for Clinical Pathology.

Case Studies

• Girard, N., Otsuji, J., Lai, L., Perry, C. S., & Fuchs, D. (2020. Sibling Donor-Derived Myeloid Sarcoma After Hematopoietic Stem Cell Transplant(pp --).