Intensive Induction Chemotherapy Followed by Early High-Dose Therapy and Hematopoietic Stem Cell Transplantation Results in Improved Outcome for Patients with Hepatosplenic T-Cell Lymphoma: A Single Institution Experience

AbstractIntroductionHepatosplenic T-cell lymphoma is a rare form of extranodal non-Hodgkin lymphoma, first recognized as a distinct entity in the Revised European-American Lymphoma classification. Typical presentation includes lymphomatous infiltration of spleen and liver, and peripheral lymphadenopathy is rarely seen. The prognosis is almost uniformly poor, and there are no prospective studies of treatment of HSTCL.Patients and MethodsFor this report, we conducted a retrospective review of all pts who underwent treatment for HSTCL at our institution. Individual chart review was performed to report clinical presentation, management, and outcome.ResultsWe identified 14 pts with HSTCL managed at our center, 7 of which remain alive with median follow-up of 65.6 months. Six of 7 received alternative induction chemotherapy regimens such as ICE (ifosfamide, carboplatin, etoposide) or IVAC (ifosfamide, etoposide, high-dose cytarabine) as opposed to CHOP and all surviving pts had proceeded to undergo either autologous or allogeneic SCT.ConclusionOur results suggest that use of non-CHOP induction regimen and early use of high dose therapy and SCT consolidation may translate to improved survival for pts with HSTCL

Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma

PIM kinase expression in human lymphomas can influence the outcome of chemotherapy, and blocking cap-dependent translation can reverse PIM-mediated rapamycin resistance in murine lymphomas

Tumor associated macrophages in relapsed and refractory Hodgkin lymphoma

Growing evidence demonstrates that an increased number of CD68 positive tumor-associated macrophages (TAM) is associated with decreased survival in patients with newly diagnosed classic Hodgkin lymphoma (HL). However, the impact of TAM in relapsed and refractory disease is unknown. To investigate whether the presence of elevated CD68 retains its prognostic significance in the relapsed and refractory setting, we analyzed pre-salvage biopsy specimens of 81 patients with relapsed and refractory HL using a tissue microarray. Scoring of CD68 was based on the percentage of CD68 positive TAM compared to the total number of cells in representative areas. The final percent of CD68 positivity for each case was based on the average of cores available for examination. In a univariate analysis, we found that patients with elevated levels of CD68 positive TAM had inferior overall survival (OS) compared with patients who had lower CD68 levels. For patients undergoing autologous stem cell transplant after salvage treatment, elevated CD68 levels were predictive of both adverse OS and event free survival. However, after adjusting for other variables, increased CD68 positive TAM did not retain prognostic significance in a multivariate model. In our dataset of primary refractory and relapsed Hodgkin lymphoma biopsy specimens, TAM infiltration is unable to definitively predict outcome. In order to validate these findings, TAM infiltration of relapsed and refractory specimens should be assessed prospectively and paired to initial Hodgkin lymphoma biopsies at diagnosis

False-Positive [ 18

Purpose Determine the clinical significance of [18F]fluorodeoxyglucose (FDG)–avid lesions in patients with lymphoma treated with stem-cell transplantation. Methods All patients who underwent stem-cell transplantation for lymphoma at Memorial Sloan-Kettering Cancer Center between January 2005 and December 2009 and had post-transplantation FDG positron emission tomography/computed tomography (PET/CT) examinations were included. PET/CT examinations were evaluated for FDG-avid lesions suggestive of disease. Clinical records, biopsy results, and subsequent imaging examinations were evaluated for malignancy. Results Two hundred fifty-one patients were identified, 107 with allogeneic and 144 with autologous stem-cell transplantation. Of allogeneic stem-cell transplantation recipients, 50 had FDG-avid lesions suggestive of lymphoma, defined as FDG-avidity greater than liver background. However, only 29 of these 50 demonstrated lymphoma on biopsy, whereas biopsy attempts were benign in the other 21 patients. Sensitivity analysis determined that a 1.5-cm short axis nodal measurement distinguished patients with malignant from nonmalignant biopsies. In 21 of 22 patients with FDG-avid lymph nodes ≤ 1.5 cm, biopsy attempts were benign. In the absence of treatment, these nodes either resolved or were stable on repeat imaging. Disease-free survival of patients with FDG-avid ≤ 1.5 cm lymph nodes was comparable with patients without FDG-avid lesions. In comparison, autologous stem-cell transplantation patients rarely demonstrated FDG-avid lesions suggestive of disease without malignant pathology. Conclusion Twenty percent (21 of 107) of patients with an allogeneic stem-cell transplantation demonstrated FDG-avid lymph nodes up to 1.5 cm in short axis on PET/CT, which did not represent active lymphoma. After allogeneic stem-cell transplantation of patients with lymphoma, benign FDG-avid ≤ 1.5 cm lymph nodes can mimic malignancy

Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma

To identify prognostic factors for patients transplanted for relapsed or refractory Hodgkin lymphoma we carried out a combined analysis of patients followed prospectively on 3 consecutive protocols at Memorial Sloan-Kettering Cancer Center. One hundred fifty-three patients with chemosensitive disease after ICE (ifosfamide, carboplatin, and etoposide)–based salvage therapy (ST) proceeded to high-dose chemoradiotherapy followed by autologous stem cell transplantation (ASCT). Patients were evaluated with computed tomography and functional imaging (gallium or fluorodeoxyglucose-positron emission tomography) prior to ST and again before ASCT. Functional imaging status before ASCT was the only factor significant for event-free survival (EFS) and overall survival by multivariate analysis and clearly identifies poor risk patients (5-year EFS 31% and 75% for FI-positive and negative patients respectively). Administration of involved-field radiotherapy with ASCT was marginally significant for EFS ( P = .055). Studies evaluating novel STs, conditioning regimens, post-ASCT maintenance, or allogeneic stem cell transplantation are warranted for patients who fail to normalize pre-ASCT functional imaging

Pre-Transplant Evaluation with Both CT and PET Following Second-Line Therapy Is Essential for Predicting Outcome in Patients with Transplant- Eligible Relapsed and Primary Refractory Hodgkin Lymphoma

Abstract The standard treatment for relapsed and primary refractory (rel/ref) Hodgkin lymphoma (HL) for patients (pts) who demonstrate chemosensitivity to second-line chemotherapy (ST) is high dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT). Since 1994, four studies at our institution evaluated ICE (ifosfamide, carboplatin, and etoposide) based salvage therapy followed by HDT-ASCT in rel/ref HL. Chemosensitivity is a requirement for pts to proceed to HDT-ASCT, however the definition of chemosensitivity is broad. We use both functional imaging (gallium or PET) and CT to assess response to ICE; pts with chemosensitive disease fall into three groups: normalization of CT and FI (NRM), residual mass on CT but with negative FI (RM, FI-), and FI positivity regardless of CT finding (FI+). Here we report the outcome for pts who responded to ICE ST and proceeded to HDT-ASCT. Between October 1994 and February 2008, 198 pts received ICE on 1 of 4 consecutive protocols (169 pts) or as per protocol (29 pts) and were deemed transplant-eligible. The median follow-up for surviving patients is 7.4 years. There were 99 male pts and 99 female pts; the median age was 31. With respect to the 3 pre-salvage chemotherapy risk factors (RF) (relapse within 1 year of primary treatment, presence of extranodal disease, and B symptoms): 44 pts had 0 RF, 64 had 1 RF, 75 had 2 RF, and 8 had 3 RF. Bulky disease defined as greater than 5cm or 10cm was present in 60 (30%) and 15 (7.5%) pts respectively. The five year event free survival (EFS) and overall survival (OS) were 69% and 78% respectively. Seventy six (38%) had a NRM response to ST, 73 (37%) had a RM, FI- response, and 49 (25%) were FI+. The 5 year EFS and OS for the three groups were 86% and 93%, 71% and 79%, and 41% and 51% respectively. There was a statistically significant improvement in OS and EFS for the NRM and RM, FI- groups compared to the FI+ group (p<0.0001). Surprisingly, a comparison between the NRM and RM, FI- groups also revealed a statistically significant improvement in EFS and OS for the NRM group (p=0.05 and 0.04 respectively). Response to ICE ST followed by HDT-ASCT is associated with a prolonged EFS and OS. The quality of response to ICE ST had a significant impact on outcome. Both a residual mass with normalized FI and abnormal FI after ST predicts for an inferior outcome following HDT-ASCT. However, residual radiotracer on FI was associated with the poorest outcome in both EFS and OS. CONCLUSION: Outcome cannot be predicted by FI alone since both RM, FI- and FI+ groups had an inferior outcome compared to NRM. The most accurate post treatment evaluation includes both CT and PET. Figure Figur