Allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of metastatic renal cell carcinoma -- single center experience

We evaluated the efficacy of allogeneic non-myeloablative stem cell transplantation (NST) in patients with metastatic renal cell carcinoma (RCC). A total of 5 patients received blood stem cells from HLA identical siblings. Conditioning consisted of: cyclophosphamide 60 mg/kg/d, days -7 to -6 and fludarabine 25 mg/m2/d for consecutive days [days -5, -4, -3, -2, -1]. The median CD34+ cell dose was 3.34 million/kg. Immunosuppression consisted of cyclosporine A and methotrexate. Among all, four patients achieved full donor chimerism with a median of 89 days. One patient rejected the graft and received the second transplantation. Grade II-III acute GVHD occured in 3 patients. None of patients achieved complete or partial response and there were only two mixed responses. All patients died due to cancer progression. There were no transplant-related deaths. Summarising, NST regimen allows allogeneic engraftment with low treatment related mortality in this high-risk population of patients. Acute and chronic GVHD are the major morbidities. Progression is common after NST in unselected patients with advanced RCC. However, regression of some metastases suggests that the graft versus tumor effect may occur after this type of treatment. At present such a procedure should be considered as an experimental approach.     

Clinicopathological features and surgical outcome of isolated metastasis of renal cell carcinoma

BACKGROUND/AIMS: The benefit of pancreatic resection for metastatic renal cell carcinoma (RCC) is poorly defined. Here, we investigate the clinicopathological features and surgical outcome of patients with pancreatic metastasis from RCC. METHODOLOGY: Among a total of 131 patients who underwent pancreatic resection at our center between November 2000 and November 2005, four patients (three men, one woman) with a median age of 57 years (range: 52-80 years) at the time of pancreatic tumor presentation, had histologically confirmed metastatic RCC to the pancreas. The medical records, imaging data, surgical records, and pathology findings of these patients were reviewed retrospectively. RESULTS: All patients underwent radical nephrectomy for primary RCC. The pathologic stage was TNM stage T2N0M0 (n = 1) or T3aN0M0 (n = 2) (no data were available on one patient). RCCs developed in the right (n = 2) or left (n = 2) kidney. The median interval between nephrectomy and detection of pancreatic metastasis was 84 months (range: 0-285 months). All patients were asymptomatic, and the pancreatic masses with a median tumor diameter of 2.0 cm (range: 1.5-4.0 cm) were detected during routine follow-up or screening examinations. All pancreatic tumors were smooth, well-demarcated, and hypervascular on imaging studies. None of them showed evidence of associated extrapancreatic disease. Complete resection with an adequate margin of safety was achieved by distal pancreatectomy (n = 3) or pylorus-preserving pancreatoduodenectomy (n = 1). Within a median follow-up period of 39 months (range: 4-41 months) after the surgery, three patients were alive with no evidence of recurrence, and one patient was alive with evidence of recurrence. The median survival from nephrectomy was 103 months (range: 40-326 months). CONCLUSIONS: RCCs may demonstrate very late metastasis to the pancreas, thus the possibility of pancreatic metastasis should be considered when a patient with a pancreatic tumor has a history of RCC, despite the interval since nephrectomy. The experience gained in this study suggests that pancreatic metastasectomy should be attempted for RCC patients without extrapancreatic disease.     

Gemcitabine and carboplatin in the treatment of locally advanced and metastatic non-small cell lung cancer

OBJECTIVE: The aim of the study was to evaluate the response, survival advantage and toxicity profile of gemcitabine-carboplatin combination cytotoxic chemotherapy in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). METHODOLOGY: Patients who received gemcitabine-carboplatin combination chemotherapy over a 2.5-years period were analyzed. Carboplatin at a dose of 5 mg/mL/min (area under the concentration-time curve) was given on day 1 and gemcitabine (1000 mg/m(2)) on days 1 and 8, every 3 weeks. RESULTS: Of 49 chemotherapy-naive patients (median age, 62 years) who received this treatment, 57% were males, 12% had stage IIIa, 39% stage IIIb and 49% metastatic disease. The Eastern Cooperative Oncology Group (ECOG) performance status of 70% of the patients was 1 at the time of commencement of chemotherapy and 2 for the remaining 30% of patients. The overall response rate, based on 33 evaluable patients, was 27.3%. The response rate was not affected by age, stage of disease or performance status. The median survival was 9 months. Median survival among patients with an ECOG performance status of 1 was 11 months, as compared with 4 months for patients with an ECOG performance status of 2 (P < 0.001). Toxicity was generally well tolerated and there were no treatment-related deaths. CONCLUSIONS: Gemcitabine-carboplatin combination chemotherapy is an effective and well-tolerated cytotoxic regimen among Malaysian patients with advanced NSCLC. A performance status of 1 or less was associated with a better survival.     

Prognostic factors of metastatic renal cell carcinoma with extensive sarcomatoid component

Purpose

To evaluate clinical characteristics including the response to targeted therapy, the benefits of cytoreductive nephrectomy, or the prognostic factors in advanced renal cell carcinoma (RCC) with extensive sarcomatoid component (ESC), a rare but fatal disease.

Methods

Data from 37 consecutive patients with metastatic or recurrent RCC with ESC (≥25 % on resected kidney or exclusive sarcomatoid histology on needle biopsy) were analyzed.

Results

Of the 37 patients, 27 patients (73 %) had synchronous metastatic disease. The median percentage of sarcomatoid component (PSC) was 50 % (range 25–93 %). Twenty (74 %) of the 27 synchronous metastatic patients underwent cytoreductive nephrectomy. Of the nine patients undergoing cytokine therapy, none showed objective responses. Two (15 %) of the 13 patients undergoing targeted agent therapy had partial responses, and five patients (38 %) achieved stable disease. The median overall survival for all patients was 5.9 months [95 % confidence interval (CI) 1.0–10.9]. In multivariate analysis, age (>58 years), ECOG performance status (>1), PSC (>50 %), and time from first diagnosis to advanced disease (<6 months) remained independent prognostic factors. Neither the type of systemic therapy nor cytoreductive nephrectomy had an effect on survival.

Conclusions

Patients with RCC with ESC have a dismal clinical course, and the majority of patients have rapid disease progression, especially in response to immunotherapy. Four clinical factors can be used to model survival outcomes for advanced RCC with ESC and may be helpful in selecting patients for aggressive treatment.     

Nonmyeloablative stem cell transplantation in metastatic renal cell carcinoma: delayed graft-versus-tumor effect is associated with chimerism conversion but transplantation has high toxicity

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4-24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.     

High-dose chemotherapy with peripheral blood progenitor cell support for patients with non-small cell lung cancer: the experience of the European Group for Bone Marrow Transplantation (EBMT) Solid Tumours Working Party

We report the experience of the EBMT Solid Tumours Working Party (STWP) using high-dose chemotherapy (HDCT) with PBPC support in patients with non-small cell lung cancer (NSCLC). Between 1989 and 2004, 36 NSCLC patients (27 men and 9 women), median age 53.5 years (range: 24-62) were treated with 63 HDCT courses. A high-dose carboplatin-based regimen was used in 53% of the cases. Thirty-two patients had relapsed/metastatic disease, while four classified as stage IIIB received HDCT followed by radiotherapy. No treatment-related death occurred. Of 25 patients who were planned to receive multi-cycle HDCT, 4 cases (16%) interrupted the treatment early due to prolonged severe toxicities and 4 (16%) due to progressive disease. Of 36 evaluable patients, 3 (8%) achieved a complete remission and 13 (36%) had a partial remission at an overall response rate of 44%. Of these, one patient with stage IIIB and one with stage IV are alive disease free at 71+ and 149+ months, respectively. After a median follow-up of 48 months (range: 6-149), median survival was 7 months (range: 1-149). Despite one anecdotal case, HDCT did not show significant activity, but induced relevant morbidity in NSCLC patients.     

Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer

Pegase 03 is a multicenter prospective randomized phase III trial evaluating the impact of first-line high-dose chemotherapy (HDC) with stem cell support on overall survival (OS), disease-free survival (DFS) and response rate in 308 patients with histologically proven metastatic breast cancer responding to induction therapy. Eligible patients received four induction cycles with FEC 100 (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)). Patients with objective response (N=179) were randomized to one cycle of HDC (cyclophosphamide 6000 mg/m(2) and thiotepa 800 mg/m(2) (CHUT)) and stem cell support (N=88), or no further treatment (N=91). All patients were observed until disease progression or death. One toxic death occurred after CHUT. Other toxicities were manageable. The response rate at 3 months was higher in the intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR) (P=0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in the intensification and the observation arms, respectively (P=0.0001). There was no survival difference: 33.6 versus 27.3% OS at 3 years (P=0.8) and 22.9 versus 22.3 months median time to relapse in the intensification and observation arms, respectively. In this randomized trial, HDC with CHUT improved DFS but not OS, corroborating findings from earlier trials.     

High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement

High-dose melphalan (HDM) plus stem cell transplantation is an effective treatment for light-chain amyloidosis (AL), but is associated with high treatment-related mortality in patients with cardiac involvement. We studied 187 patients with cardiac involvement with AL who underwent HDM between 1996 and 2008. The median age was 57 years and the median time from diagnosis to HDM was 3.6 months. Half of the patients received reduced-dose melphalan (100-160 mg/m(2)). The median overall survival (OS) was 66 months, 54 months from diagnosis and HDM, respectively, and 91 patients (49%) were alive at the last follow-up 52 months (median) from HDM. Thirty patients (16%) died within 100 days of transplantation; only low serum albumin predicted early deaths. Overall, hematologic response (HR) and cardiac responses were seen in 66% and 41% of patients, respectively. The median OS for patients with and without HR was not reached and 22 months, respectively (P < .01); and for those with any decrease and no decrease in N-terminal-pro-brain natriuretic peptide was not reached and 26 months, respectively (P < .01). In multivariate analysis of baseline factors, only reduced-dose melphalan predicted shorter OS. HDM is feasible in patients with cardiac amyloidosis, and achievement of HR and organ response is associated with improved survival.     

Clinical responses following nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma are associated with expansion of CD8+ IFN-gamma-producing T cells

Nonmyeloablative allogeneic stem cell transplantation (NST) is thought to be an immunologic therapy in which donor T cells mediate a graft-versus-tumor effect. We recently reported the clinical outcome of a phase II trial of NST in metastatic renal cell carcinoma (RCC). However, the immune response correlates of clinical activity remain unknown. We now describe the analysis of T-cell subsets and T-cell cytokine-producing potential for those patients evaluable for immune monitoring. The incidence of graft-versus-host disease (GVHD) correlated with clinical outcome, with all responders exhibiting chronic GVHD. Following initial tapering of immunosuppression, an increase in the total numbers of CD8+ T cells but not CD4+ T cells was observed among responders compared to nonresponders. In addition, a greater ratio of CD8+ to CD4+ T cells producing IFN-gamma and IL-2 was seen in clinical responders at the time when clinical responses were first detected (day 180 after transplantation). Our results support the hypothesis that the antitumor effects of NST may be mediated by IFN-gamma-producing CD8+ T cells, and indicate that isolation of putative tumor antigen-specific T cells, ideally, should be pursued around day +180.     

A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LHRH analog in androgen ablation-refractory prostate cancer patients.

We evaluated whether the combination of triptorelin, a LHRH analog (LHRH-A), with dexamethasone and lanreotide, a somatostatin analog, can produce objective clinical responses in metastatic androgen ablation-refractory prostate cancer (stage D3) patients who have relapsed, after combined androgen blockade (LHRH-A plus antiandrogen) and antiandrogen withdrawal. Eleven stage D3 patients with diffuse bony metastases, who had progressed despite initial responses (lasting <12 months) to combined androgen blockade therapy and subsequently failed antiandrogen withdrawal, received oral dexamethasone (4 mg daily for the first month, tapered down to 2 mg after the first month and 1 mg after the second month, and continued on 1 mg thereafter) and lanreotide (30 mg im every 14 d) in combination with triptorelin (3.75 mg im every 28 d). Serum prostate-specific antigen, alkaline phosphatase, performance status, and bone pain were assessed monthly during therapy. Fasting blood glucose was measured biweekly, and serum IGF-I, T, and dehydroepiandrosterone sulfate levels were assessed at baseline, at response to the combination therapy, and at relapse from it. Ten of 11 stage D3 patients [90.9% of patients; 95% confidence interval (CI), 58.7-99.8%] had durable objective clinical responses (including > or = 50% prostate-specific antigen decline in 8 patients, 72.7%; 95% CI, 39-94%). All patients reported significant and durable improvement of bone pain (for a median duration of 13 months; 95% CI, 12-14 months; range, 6-22 months) and performance status (median duration, 19 months; 95% CI, 13-25 months; range, 7-22 months) without major treatment-related side effects. The median progression-free survival was 7 months (95% CI, 4-10 months; range, 3-17 months), and the median overall survival was 18 months (95% CI, 16-20 months; range, 7-22 months). Five of six total deaths occurred secondary to disease progression. We observed a statistically significant (P = 0.018) reduction in serum IGF-I levels at response to the combination therapy (60% reduction of baseline IGF-I levels). Dehydroepiandrosterone sulfate levels, although already significantly suppressed at baseline, had an additional significant reduction (P < 0.02) at response to therapy. T levels remained suppressed within castration levels (<3 nmol/liter, at baseline and throughout therapy, including relapse). The combination therapy of LHRH-A with dexamethasone plus somatostatin analog produces objective clinical responses and symptomatic improvement in androgen ablation (LHRH-A) refractory prostate cancer patients.     

Metastatic breast cancer confined to the skeletal system. An indolent disease

The records of 86 patients with metastatic breast cancer confined to the skeletal system were retrospectively reviewed to evaluate the clinical impression that this subset of patients with metastatic breast cancer has a favorable prognosis. The median survival for this group of patients was 48 months, compared with a median survival of 17 months in patients with breast cancer metastatic to other sites (p less than 0.01). Systemic treatment with either hormonal therapy or chemotherapy was highly effective in these patients; 56 of 64 (87 percent) showed response to the first hormonal therapy received (median, 10 months; range, four to 54 months), and 43 of 46 (93 percent) showed response to initial chemotherapy (median, 11 months; range, six to 22 months). Most patients received several therapeutic modalities sequentially; sequential responses to hormonal therapy were frequent. Orthopedic complications were common (pathologic fracture in 18; epidural spinal cord compression in 13) and occurred a median of 24 months after documentation of bone metastasis. Prolonged survival was common after these complications (median, 18 months; range, two to 48 months). The presence of metastatic disease at the time of diagnosis and premenopausal status were not adverse prognostic factors. Metastases often remained localized to the skeleton; however, appearance of extraskeletal metastasis was associated with short subsequent survival (median, nine months). Metastatic breast cancer confined to the skeletal system is a common entity that can be defined clinically, is highly responsive to treatment, and is frequently associated with prolonged survival.     

Autologous stem cell transplantation in primary systemic amyloidosis: the impact of selection criteria on outcome

Autologous stem cell transplantation (ASCT) for primary systemic amyloidosis (AL) produces high hematologic and organ responses. However, treatment-related mortality remains high and reported series are subject to selection bias. In all, 48 of 80 amyloid patients referred to our center had AL in the absence of myeloma, 26 of these 48 were deemed transplant candidates and 20 actually underwent ASCT. Transplant-related mortality has fallen from 50 to 20% since January 1999 due to better patient selection and prophylactic measures. Intent-to-treat organ responses were renal (46%), cardiac (25%) and liver (50%). Organ responses in patients who survived transplantation were renal (75%), cardiac (40%) and liver (100%). The 3-year OS post-ASCT was 56% with improved outcome predicted by a better performance status (P=0.08), normal ALP (P=0.08), nephrotic syndrome (P=0.01) and the absence of severe hypotension (P=0.01). The 3-year OS for all referred patients was 44% and this was not significantly better for transplant candidates. Patients with significant hypotension (systolic blood pressure < or =90 mmHg) or poor performance status (ECOG >2) have an exceedingly high treatment-related mortality and should not be transplanted. For those undergoing ASCT, organ response rates appear promising, but conclusive evidence of improved survival for this select group of patients is still lacking and will require randomized trials.     

A multi-institution analysis of outcomes of liver-directed surgery for metastatic renal cell cancer

Objectives

Management of liver metastasis (LM) from a non-colorectal, non-neuroendocrine primary carcinoma remains controversial. Few data exist on the management of hepatic metastasis from primary renal cell carcinoma (RCC). This study sought to determine the safety and efficacy of surgery for RCC LM.

Methods

A total of 43 patients who underwent surgery for RCC hepatic metastasis between 1994 and 2011 were identified in a multi-institution hepatobiliary database. Clinicopathologic, operative and outcome data were collected and analysed.

Results

Mean patient age was 62.4 years and most patients (67.4%) were male. The mean tumour size of the primary RCC was 6.9 cm and most tumours (72.1%) were designated as clear cell carcinoma. Nine patients (20.9%) presented with synchronous LM. Among the patients with metachronous disease, the median time from diagnosis of the primary RCC to treatment of LM was 17.2 months (range: 2.1–189.3 months). The mean size of the RCC LM was 4.0 cm and most patients (55.8%) had a solitary metastasis. Most patients (86.0%) underwent a minor resection (up to three segments). Final pathology showed margin status to be negative (R0) in 95.3% of patients. Postoperative morbidity was 23.3% and there was one perioperative death. A total of 69.8% of patients received perioperative chemotherapy. Overall 3-year survival was 62.1%. Three-year recurrence-free survival was 27.3% and the median length of recurrence-free survival was 15.5 months.

Conclusions

Resection of RCC hepatic metastasis is safe and is associated with low morbidity and near-zero mortality. Although recurrence occurs in up to 50% of patients, resection can be associated with long-term survival in a well-selected subset of patients.     

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.     

CCNU, vincristine, methotrexate, and procarbazine treatment of relapsed small cell lung carcinoma

Thirty-two patients with refractory relapsed small cell carcinoma of the lung (SCCL) were treated with a combination of CCNU (lomustine), vincristine, methotrexate, and procarbazine (COMP); 29 were evaluable for response. Nine patients (31%) had responses: five complete responses (CR) and four partial responses. Patients with CR had a median survival of 11 months (range, 51/2-141/2) from the start of COMP. Patients with less than CR had a median survival of approximately 3 months (range, less than 1-7). The comparison of CR versus less than CR is significant (P = 0.003). Patients achieving CR usually had limited disease and four of the five who achieved CR survived greater than 6 months. The regimen was well-tolerated, but myelosuppression was seen in all patients. COMP appears to be a useful combination in patients with relapsed SCCL. Aggressive retreatment should be considered in relapsed patients with this disease since some may achieve a second CR, with the associated potential survival benefit.     

Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age

Nonmyeloablative stem cell transplantation (NST) is increasingly used in older patients. The impact of the shift from myeloablative transplantation to NST on relapse, transplant complications, and outcome has yet to be fully examined. We performed a retrospective analysis of 152 patients older than 50 years undergoing NST or myeloablative transplantation. Seventy-one patients received nonmyeloablative conditioning, fludarabine (30 mg/m(2)/d x 4) and intravenous busulfan (0.8 mg/kg/d x 4); 81 patients received myeloablative conditioning, primarily cyclophosphamide and total body irradiation. NST patients were more likely to have unrelated donors (58% versus 36%; P = .009), a prior transplant (25% versus 4%; P = < .0001), and active disease at transplantation (85% versus 59%; P = < .001). Despite the adverse characteristics, overall survival was improved in the NST group at 1 year (51% versus 39%) and 2 years (39% versus 29%; P = .056). There was no difference in progression-free survival (2 years, 27% versus 25%; P = .24). The incidence of grade 2 to 4 graft-versus-host disease was similar (28% versus 27%). The nonrelapse mortality rate was lower for NST patients (32% versus 50%; P = .01), but the relapse rate was higher (46% versus 30%; P = .052). Our experience suggests that, in patients over age 50, NST with fludarabine and low-dose busulfan leads to an overall outcome at least as good as that following myeloablative therapy.     

Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT

Autologous SCT (ASCT) remains an effective therapy for eligible patients with myeloma. Previous studies have suggested a lack of impact of the initial therapy on the outcome after ASCT. It is not clear if incorporation of new agents in the initial treatment regimens will have any impact on the outcome after ASCT. We studied 472 patients undergoing ASCT within 12 months of diagnosis to assess the effect of initial therapy on the outcome after ASCT. Patients received initial therapy with vincristine, adriamycin and dexamethasone (VAD), dexamethasone, thalidomide and dexamethasone or lenalidomide and dexamethasone. While patients treated with dexamethasone alone had higher disease burden at ASCT, no differences were observed in the response rates to ASCT, post transplant complications or treatment-related mortality among the groups. The median time to progression after ASCT was 27.1, 24.7, 21.1 months and did not reach the VAD, Dex, Thal-Dex and Len-Dex group, respectively, P=0.11. The median overall survival from ASCT was 62 months for VAD, 69.6 months for Dex and were not reached for Thal-Dex and Len-Dex groups, P=0.2. For patients undergoing early ASCT for myeloma, the nature of initial treatment utilized has no long-term impact on the outcome of ASCT.     

Sequential high-dose methotrexate, 5-fluorouracil,and doxorubicin for treatment of advanced pancreatic cancer

Summary A phase II trial of sequential high-dose methotrexate, 1500 mg/m², and 5-fluorouracil, 1500 mg/m² intravenously on day 1, plus doxorubicin, 30 mg/m² i. v. on day 14, has been undertaken in patients with locally advanced or metastatic adenocarcinoma of the pancreas. Of 25 evaluable patients there were 1 complete response and 3 partial responses for an overall response rate of 16% (95% confidence interval 5%–36%). The median survival of all patients was 6.7 months (range 1–17 months). There was one treatment-related death due to pancytopenia and sepsis. In all other patients therapy was generally well-tolerated. We conclude that this combination protocol has only modest activity in the treatment of advanced pancreatic cancer.     

Analysis of donor-type chimerism in lineage-specific cell populations after allogeneic myeloablative and non-myeloablative stem cell transplantation

We analyzed donor-type chimerism in CD3+, CD14.15+ and CD56+ cells from 36 patients who had undergone conventional-intensity allogeneic stem cell transplantation (CST) and 34 patients who had undergone non-myeloablative allogeneic stem cell transplantation (NST) for hematological malignancies. On day 28 after transplantation, all fractions in NST patients and CD3+ cells in CST patients who received a non-total body irradiation (TBI) regimen showed more frequent mixed chimerism (<90% donor cells) than those in patients who had received TBI. NST patients with acute graft-versus-host disease (grade II-IV) frequently showed more than 50% donor-type chimerism in CD3+ cells on day 14 (P=0.029). NST patients with <50% donor-type chimerism on day 14 and with <90% donor-type chimerism on day 28 in CD56+ cells had significantly poor 1-year overall survival (0 vs 91%, P<0.001 and 20 vs 74%, P=0.002, respectively). Both NST and CST patients with <90% donor-type chimerism in CD14.15+ cells on day 28 had significantly poor 1-year overall survival (14 vs 70%, P=0.005 and 0 vs 66%, P=0.002, respectively). Our data show that the extent of donor-type chimerism in lineage-specific cells appears to have an impact on outcome after allogeneic stem cell transplantation.     

Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum

The median survival of all patients with hepatic metastases from colorectal cancer referred to the Sidney Farber Cancer Institute during a five-year period was 12.5 months. Two major factors influenced survival. The first was extent of disease at presentation. The second was the histologic grade of the cancer. The median survival of patients presenting with the least disease, characterized by less than four liver nodules visible on liver scan (n=38), normal liver size on physical examination (n=60), normal liver function test results (n=30), and normal performance status (n=91), was between 18 and 24 months, regardless of treatment. The median survival of those few patients (n=13) who had objective responses to a variety of treatments, most of whom also had minimal disease at presentation, was also 24 months. Patients whose tumors were poorly differentiated or who had abnormal performance status or weight loss of greater than 10 per cent at presentation survived only six months (median). Those with four or more liver nodules, hepatomegaly (greater than 16-cm vertical span on physical examination), or abnormal liver function test results, survived ten, eight, and 12 months (median), respectively. It is concluded that a significant group of patients survived longer than would have been predicted by earlier literature surveys after the diagnosis of colorectal cancer metastatic to the liver. It is suggested that future therapeutic trials, using survival as a measure of response of patients with liver metastases from colorectal cancer, must be prospectively controlled before selection factors can be differentiated from significant therapy effect. Supported by the Brigham Surgical Group, Inc., and National Cancer Institute grant CA 04486.