Bowel perforation in intestinal lymphoma: incidence and clinical features.

BACKGROUND: Perforation is a serious life-threatening complication of lymphomas involving the gastrointestinal (GI) tract. Although some perforations occur as the initial presentation of GI lymphoma, others occur after initiation of chemotherapy. To define the location and timing of perforation, a single-center study was carried out of all patients with GI lymphoma. PATIENTS AND METHODS: Between 1975 and 2012, 1062 patients were identified with biopsy-proven GI involvement with lymphoma. A retrospective chart review was undertaken to identify patients with gut perforation and to determine their clinicopathologic features. RESULTS: Nine percent (92 of 1062) of patients developed a perforation, of which 55% (51 of 92) occurred after chemotherapy. The median day of perforation after initiation of chemotherapy was 46 days (mean, 83 days; range, 2-298) and 44% of perforations occurred within the first 4 weeks of treatment. Diffuse large B-cell lymphoma (DLBCL) was the most common lymphoma associated with perforation (59%, 55 of 92). Compared with indolent B-cell lymphomas, the risk of perforation was higher with aggressive B-cell lymphomas (hazard ratio, HR = 6.31, P < 0.0001) or T-cell/other types (HR = 12.40, P < 0.0001). The small intestine was the most common site of perforation (59%). CONCLUSION: Perforation remains a significant complication of GI lymphomas and is more frequently associated with aggressive than indolent lymphomas. Supported in part by University of Iowa/Mayo Clinic SPORE CA97274 and the Predolin Foundation.

Time of relapse after initial therapy significantly adds to the prognostic value of the IPI-R in patients with relapsed DLBCL undergoing autologous stem cell transplantation.

We explored the concomitant effect of the International Prognostic Index at the time of relapse (IPI-R) and the time from initial diagnosis to relapse (TTR) on outcome of 80 uniformly treated patients receiving BEAM conditioning followed by SCT for relapsed, chemosensitive diffuse large B-cell lymphoma. Median age at the time of transplantation was 62 years (range 26-77). Median follow-up of survivors was 31.4 months. Median overall survival (OS) from the time of transplant for patients with TTR >18 months vs < or =18 months was not reached and 50 months, respectively (P=0.01). Median OS for patients with IPI-R > or =3 was 23.3 months and not reached for patients with IPI-R <3 (P=0.01). These factors were independent in multivariate analysis with relative risk for death of 0.91 (0.80-0.99; P=0.04) for each 6-month increment in TTR and 0.63 (0.42-0.96; P=0.03) for IPI-R <3. TTR < or =18 months and IPI-R > or =3 were combined in a prognostic system where patients with none (n=32), one (n=39) or two (n=9) of these factors had median OS not reached, of 50 and 5 months, respectively (P<0.01). Patients with early, high IPI-R relapse after first-line therapy have a dismal outcome with SCT and should receive experimental therapies.

Infusion of autograft natural killer cell/CD14+HLA-DRDIM cell ratio predicts survival in lymphoma post autologous stem cell transplantation.

The infusion of autograft absolute lymphocyte count (A-ALC) and autograft natural killer cells (A-NKC) are prognostic factors for overall survival (OS) and PFS in non-Hodgkin's lymphoma (NHL) patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). The human monocytic CD14+HLA-DRDIM cells are associated with worse prognosis in NHL. Thus, we investigated whether the autograft A-NKC/A-CD14+HLA-DRDIM ratio predicts survival in NHL. In a total of 111 NHL patients, we analyzed apheresis collection samples for the content of A-NKC and A-CD14+HLA-DRDIM. With a median follow-up of 57.2 months (range: 2.1-84.6 months), patients with an A-NKC/A-CD14+HLA-DRDIM ratio of ⩾0.29 experienced superior OS (5-year OS rates of 84% (95% confidence interval (CI), 72-91%) vs 48% (95% CI, 34-62%), P<0.0002, respectively) and PFS (5-year PFS rates of 59% (95% CI, 47-71%) vs 32% (95% CI, 20-48%), P<0.002, respectively). Multivariate analysis revealed that A-NKC/A-CD14+HLA-DRDIM ratio was an independent predictor for PFS (hazard ratio (HR)=0.56, 95% CI, 0.32-0.96, P<0.03) and OS (HR=0.34, 95% CI, 0.16-0.68, P<0.002). The A-NKC/A-CD14+HLA-DRDIM ratio provides a platform to target specific autograft immune effector cells to improve clinical outcomes in NHL patients undergoing APBHSCT.

Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia.

Absolute lymphocyte count (ALC) recovery postautologous stem cell transplantation is an independent predictor for survival in acute myelogenous leukemia (AML). The role of ALC recovery after induction chemotherapy (IC) in AML is unknown. We hypothesize that ALC recovery after IC has a direct impact on survival. We have now evaluated the impact of ALC recovery after IC on overall survival (OS) and leukemia-free survival (LFS) in 103 consecutive, newly diagnosed AML patients treated with standard IC and consolidation chemotherapy (CC) from 1998 to 2002. ALC recovery was studied at days 15 (ALC-15), 21 (ALC-21), 28 (ALC-28) after IC and before the first CC (ALC-CC). Superior OS and LFS at each time point were observed with an ALC-15, ALC-21, ALC-28, and ALC-CC > or = 500 cells/microl. Patients with an ALC > or = 500 cells/microl at all time points vs those who did not have superior OS and LFS (not reached vs 13 months, P<0.0001; and not reached vs 11 months, P<0.0001, respectively). Multivariate analysis demonstrated ALC > or = 500 cells/microl at all time points to be an independent prognostic factor for survival. Our data suggest a critical role of lymphocyte (immune) recovery on survival after IC in AML.

Prognostic relevance of lymphocytopenia, monocytopenia and lymphocyte-to-monocyte ratio in primary myelodysplastic syndromes: a single center experience in 889 patients.

Current prognostic models for myelodysplastic syndromes (MDS), including the Revised International Prognostic Scoring System (IPSS-R), do not account for host immunity. We retrospectively examined the prognostic relevance of monocytopenia, lymphocytopenia and lymphocyte-to-monocyte ratio (LMR) in a cohort of 889 patients with primary MDS. After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformation were documented. In univariate analysis, subnormal absolute lymphocyte count (ALC) <0.9 × 109/l; P=0.001), ALC<1.2 × 109/l (P=0.0002), subnormal absolute monocyte count (AMC) <0.3 × 109/l (P=0.0003), LMR (P⩽0.0001) and LMR⩾5 (P=0.03) were all associated with inferior overall survival. In multivariable analysis that included other risk factors, significance was retained for LMR (P=0.02) and became borderline for ALC <1.2 × 109/l (P=0.06). Analysis in the context of IPSS-R resulted in P-values of 0.06 for ALC<1.2 × 109/l, 0.7 for monocytopenia and 0.2 for LMR. Leukemia-free survival was not affected by ALC, AMC or LMR. The observations from the current study suggest a possible detrimental role for altered host immunity in primary MDS, which might partly explain the therapeutic benefit of immune-directed therapy, including the use of immune modulators; however, IPSS-R-independent prognostic value for either ALC or AMC was limited.

A phase 1 trial of 90Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma.

This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (90Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m2 with indium-111 ibritumomab tiuxetan (111In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m2 with escalating doses of 90Y-Zevalin (day -14); melphalan 100 mg/m2 (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient's 111In-Zevalin dosimetry data were used to calculate the dose of 90Y-Zevalin (in mCi) to deliver 10, 12, 14, 16, 18 or 20 Gy to the liver. Dose limiting toxicities were seen in 3 patients. The overall response rate was 73% (22/30) with stringent complete response in 2 patients; complete response, 5; very good partial response, 12; and partial response, 3. The median PFS was 16.5 months and the median overall survival was 63.4 months. In MM, the MTD of 90Y-Zevalin with HDM is 18 Gy to the liver. The addition of radiation with novel delivery methods such as radioimmunotherapy combined with standard transplant regimens warrants further study.

Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma.

Autologous stem cell transplantation (ASCT) is an effective treatment strategy for mantle-cell lymphoma (MCL) demonstrating significantly prolonged progression-free survival (PFS) when compared to interferon-alpha maintenance therapy of patients in first remission. The study of absolute lymphocyte count at day 15 (ALC-15) after ASCT as a prognostic factor in non-Hodgkin lymphoma (NHL) included different lymphoma subtypes. The relationship of ALC-15 after ASCT in MCL has not been specifically addressed. We evaluated the impact of ALC-15 recovery on survival of MCL patients undergoing ASCT. We studied 42 consecutive MCL patients who underwent ASCT at the Mayo Clinic in Rochester from 1993 to 2005. ALC-15 threshold was set at 500 cells/microl. The median follow-up after ASCT was 25 months (range, 2-106 months). The median overall survival (OS) and PFS times were significantly better for the 24 patients who achieved an ALC-15 >or=500 cells/microl compared with 18 patients with ALC-15 <500 cells/microl (not reached vs 30 months, P<0.01 and not reached vs 16 months, P<0.0006, respectively). Multivariate analysis demonstrated ALC-15 to be an independent prognostic factor for OS and PFS. The ALC-15 >or=500 cells/microl is associated with a significantly improved clinical outcome following ASCT in MCL.

Apheresis instrument settings influence infused absolute lymphocyte count affecting survival following autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin's lymphoma: the need to optimize instrument setting and define a lymphocyte collection target.

Autograft absolute lymphocyte count (A-ALC) is an independent prognostic factor for survival after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) for non-Hodgkin's lymphoma (NHL). Factors enhancing A-ALC collections are unknown. We hypothesize that apheresis instrument settings could affect A-ALC. Data from 127 NHL patients collected from 15 January 1999 to 30 July 2004 using a single apheresis instrument (COBE Spectra (SP), Baxter Amicus (AM), and CS3000 Plus (CS)) were analyzed. The primary end point of the study was to assess the correlation between apheresis instrument settings and A-ALC. The secondary end point was to determine the effect of apheresis instrument on survival post-APHSCT. Patients collected using SP achieved higher A-ALC compared to AM (with modified settings) or CS (P<0.05) and demonstrated superior overall (OS) and progression-free survival (PFS) (P<0.03). Multivariate analysis demonstrated A-ALC and not the apheresis instrument as an independent prognostic factor for OS and PFS, cancelling the prognostic effect of the apheresis instruments observed in the univariate analysis. The survival advantage observed by SP was from the higher A-ALC collected compared to AM and CS. These data suggest that apheresis instrument settings should be optimized to collect CD34(+) cells as well as an A-ALC target, with direct impact on survival post-APHSCT.

Autologous hematopoietic stem cell transplantation for older patients with relapsed non-Hodgkin's lymphoma.

To evaluate autologous stem cell transplant (ASCT) in older patients with intermediate grade non-Hodgkin's lymphoma (NHL), the Mayo Clinic Rochester BMT database was reviewed for all patients 60 years of age and older who received ASCT for NHL between September 1995 and February 2003. Factors evaluated included treatment-related mortality (TRM), event-free survival (EFS) and overall survival (OS). Ninety-three patients were identified, including twenty-four (26%) over the age of 70 years. Treatment-related mortality (5.4%) was not significantly different when compared to a younger cohort (2.2%). At a median follow-up of 14 months (0.6-87.6 months), the estimated median survival is 25 months (95% confidence interval (CI) 12-38) in the older group compared to 56 months (95% CI 37-75) (P=0.037) in the younger group. The estimated 4-year EFS was 38% for the older group compared to 42% in the younger cohort (P=0.1). By multivariate analysis, the only factor found to influence survival in the older group was age-adjusted International Prognostic Index at relapse, 0-1 better than 2-3 (P=0.03). Autologous stem-cell transplant can be safely performed in patients 60 years or older with chemotherapy sensitive relapsed or first partial remission NHL. The outcome may not be different from that of younger patients in terms of TRM and EFS.

Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia.

Prognosis in chronic myelomonocytic leukemia (CMML) is unfavorable and the optimal therapy remains uncertain. Currently, allogeneic stem cell transplantation is the only known curative therapeutic option. However, the data available are limited and restricted to small retrospective series. There is even less information on the use of donor lymphocyte infusions (DLI) for this disease. We reviewed our experience of allogeneic stem cell transplantation and DLI for adults with CMML. Seventeen consecutive adults underwent allogeneic stem cell transplantation from related (n=14) or unrelated (n=3) donors. Median age was 50 years (range 26-60). Seven patients (41%) demonstrated relapse or persistent disease at a median of 6 months (range 3-55.5). Five patients underwent DLI for morphologic relapse and one for mixed donor chimerism. Two patients achieved durable complete remissions of 15 months each. The overall transplant-related mortality was 41% (n=7). With a median follow-up of 34.5 months, three patients (18%) currently remain alive and in continuous CR. The current study demonstrates a graft-versus-leukemia effect in CMML, both for allogeneic stem cell transplantation and for DLI. Nevertheless, consistent with reported experience of others, overall outcomes remain less than optimal and unpredictable.

Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia.

Absolute lymphocyte count (ALC) recovery correlates with survival after autologous hematopoietic stem cell transplantation (AHSCT) for patients with multiple myeloma, non-Hodgkin's lymphoma, and metastatic breast cancer. The role of ALC recovery in relationship to clinical outcome after AHSCT in patients with acute myelogenous leukemia is unknown. We analyzed 45 patients who underwent AHSCT at Mayo Clinic, Rochester, Minnesota between 1990 and 2000. The ALC threshold was selected at 500 cells/microl on day 15 post-AHSCT based on our previous studies. Thirty-two females and 13 males were included in the study with a median age of 45 years (range 12-75). The median follow-up was 14 months with a maximum of 129 months. The median overall and leukemia-free survival were significantly better for the 23 patients with ALC at day 15 > or =500 cells/microl compared with 22 patients with ALC <500 cells/microl (not yet reached vs 10 months, P < 0.0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC > or =500 cells/microl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies.

The dose of infused lymphocytes in the autograft directly correlates with clinical outcome after autologous peripheral blood hematopoietic stem cell transplantation in multiple myeloma.

Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in multiple myeloma (MM); however, factors affecting ALC-15 in MM remain unknown. We hypothesized that the dose of infused peripheral blood autograft lymphocytes (autograft absolute lymphocyte count: A-ALC) impacts ALC-15 recovery. Between 1989 and 2001, 267 consecutive MM patients underwent APHSCT. We set out to determine the correlation between A-ALC and ALC-15 and the utility of A-ALC as a marker for ALC-15 recovery. A-ALC was found to be both a strong predictor for area under curve (AUC=0.93; P=0.0001) and strongly correlated with (r(s)=0.83; P=0.0001) ALC-15 recovery. Higher infused A-ALC was significantly correlated with an ALC-15>/=500/microl. In addition, median post-transplant overall survival (OS) and time to progression (TTP) were longer in patients who received an A-ALC>/=0.5 x 10(9) lymphocytes/kg versus A-ALC <0.5 x 10(9) lymphocytes/kg (58 vs 30 months, P=0.00022; 22 vs 15 months, P<0.00012, respectively). Multivariate analysis demonstrated A-ALC as an independent prognostic indicator for OS and TTP. These results indicate that an infused dose of autograft lymphocytes significantly impacts clinical outcome post-APHSCT in MM.

IL-10 induces the development of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell non-Hodgkin lymphoma.

The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14(+)HLA-DR(low/-) phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14(+)HLA-DR(low/-) monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4(+)HLA-DR(low/-) population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14(+) monocytic cells with an HLA-DR(low/-) phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14(+)HLA-DR(low/-) population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14(+)HLA-DR(low/-) population. Furthermore, we found that IL-10-induced CD14(+)HLA-DR(low/-) monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell NHL.

Immune reconstitution after autologous hematopoietic stem cell transplantation.

Autologous hematopoietic stem cell transplantation has proved to be an effective treatment for certain hematologic malignancies. However, relapse rates are high during the first year after transplantation. These relapses are attributed to the failure of high-dose chemotherapy to eradicate minimal residual malignant disease. In allogeneic hematopoietic stem cell transplantation, the higher antitumor effects observed compared with those in autologous hematopoietic stem cell transplantation are based on the immunologically mediated graft-vs-tumor effect. Therefore, a better understanding of the mechanisms involved in immune reconstitution after hematopoietic stem cell transplantation may clarify the importance of various components of the recovery of the immune system as they pertain to eradication of residual tumor, as well as uncover possible interventions directed at maximizing this effect. This review focuses on immune reconstitution after autologous hematopoietic stem cell transplantation. Autologous hematopoietic stem cell transplantation is not affected by graft-vs-host disease or immunosuppressive therapy after transplantation to control graft-vs-host disease, providing a direct insight into the mechanisms involved in immune reconstitution after engraftment.

Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer.

Early absolute lymphocyte count (ALC) recovery at day 15 post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival in multiple myeloma and non-Hodgkin's lymphoma. The relationship of ALC with clinical outcomes in metastatic breast cancer is unknown. We evaluated all 29 patients with metastatic breast cancer who underwent ASCT at the Mayo Clinic, Rochester, Minnesota, from 1994 to 1999. The ALC threshold was set at 500 cells/microl on day 15 post-ASCT based on previous experience with hematologic malignancies. All patients were followed for a minimum of 2 years or until death, with a median follow-up for living patients of 2.25 years. Of the 29 patients, 17 have died with disease progression, two are alive and have progressed, and 10 are alive without progression. The median overall and progression-free survival times were significantly better for the 20 patients with ALC > or = 500 cells/microl compared with the nine patients with ALC <500 cells/microl (not reached vs 14 months, P < 0.0001; 24 vs 7 months, P < 0.0015, respectively). In conclusion, ALC > or = 500 cells/microl on day 15 post-ASCT was associated with significantly better survival in patients with metastatic breast cancer, suggesting the importance of early immune recovery post-ASCT in these patients.

Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-alpha in autologous stem cell transplantation.

High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Preclinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-alpha enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-alpha to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-alpha and IL-2 at 10000 IU/ml. NK cell activity was determined by sodium chromate (51)Cr release assay for lysis of K562 target cells. IL-2 and IFN-alpha each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-alpha up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.

Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate.

High-dose chemotherapy and autologous stem cell transplantation are used increasingly to treat patients with light-chain-related amyloidosis (AL). Treatment-related mortality is approximately 15%. To enable more patients to undergo stem cell transplantation, a risk-adapted strategy has been developed to treat with lower chemotherapy doses those patients who are at excessive risk. It is unclear whether reducing the chemotherapy dose in patients at excessive risk of treatment toxicity reduces the overall response. We retrospectively reviewed 171 AL patients who underwent conditioning chemotherapy with stem cell transplantation. The patients comprised two groups: those receiving standard high-dose melphalan and those receiving intermediate-dose melphalan. Responses were categorized as hematologic response, which used criteria for myeloma response. The two groups showed statistically significant differences; the overall response rates were 75% in the high-dose group and 53% in the intermediate-dose group although treatment-related mortality was the same in both groups. Reducing the melphalan dose appeared to render more AL patients eligible for stem cell transplantation but sacrificed an element of response. Methods are needed to reduce treatment-related toxicity so that more patients can receive full-dose conditioning chemotherapy.

Infused peripheral blood autograft absolute lymphocyte count correlates with day 15 absolute lymphocyte count and clinical outcome after autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin's lymphoma.

Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in non-Hodgkin's lymphoma (NHL). Factors affecting ALC-15 remain unknown. We hypothesized that dose of infused autograft lymphocytes (A-ALC) directly impacts upon ALC-15. A total of 190 consecutive NHL patients received A-ALC between 1993 and 2001. The primary end point was correlation between A-ALC and ALC-15. A strong correlation was identified (r=0.71). A higher A-ALC was infused into patients achieving an ALC-15 > or =500/microl vs ALC-15 <500/microl (median of 0.68 x 10(9)/kg (0.04-2.21 x 10(9)/kg), vs 0.34 x 10(9)/kg (0.04-1.42 x 10(9)/kg), P<0.0001). The median follow-up for all patients was 36 months (maximum of 109 months). The A-ALC threshold was determined at 0.5 x 10(9)/kg. The median overall survival (OS) and progression-free survival (PFS) times were longer in patients who received an A-ALC >/=0.5 x 10(9)/kg vs A-ALC <0.5 x 10(9)/kg (76 vs 17 months, P<0.0001; 49 vs 10 months, P<0.0001, respectively). Multivariate analysis demonstrated A-ALC to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that ALC-15 and survival are dependent upon the dose of infused A-ALC in NHL.

Timely reconstitution of immune competence affects clinical outcome following autologous stem cell transplantation.

The anti-tumor activity of the immune system in the setting of hematopoietic stem cell transplantation has largely been described in the context of the "graft-versus-tumor" effect of allogeneic stem cell transplantation. This article reviews clinical evidence suggesting the existence of an autologous graft-versus-tumor effect in the setting of host immune system recovery following autologous stem cell transplantation resulting in prolongation of survival of cancer patients.

Idiopathic thrombocytopenic purpura associated with breast cancer: a case report and review of the current literature.

The association of solid tumors with idiopathic thrombocytopenic purpura (ITP) is rare. Before this study, there have been three case reports indicating an association between breast cancer and ITP. We present a 69-year-old man with metastatic breast cancer and progressive thrombocytopenia without any evidence of a leukoerythroblastic picture or etiologies for the thrombocytopenia. Serum platelet antibodies were identified. A bone marrow biopsy showed small foci of metastatic breast cancer, thrombocytopenia, and normal number of megakaryocytes. A subsequent trial of steroids resulted in a marked improvement of the patient's thrombocytopenia. This is the fourth case report indicating an association of breast cancer and ITP.