Jacob D. Bitran

Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma.

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference in response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.

High-dose consolidation therapy with autologous stem-cell rescue in stage IV breast cancer: follow-up report.

PURPOSE Fifty-nine patients with newly diagnosed metastatic breast cancer were treated with induction chemotherapy followed by high-dose intensification and autologous stem-cell rescue (ASCR) to determine therapeutic efficacy. PATIENTS AND METHODS Induction consisted of cyclophosphamide, doxorubicin, vincristine, and methotrexate with leucovorin rescue (LOMAC) in 27 patients, or fluorouracil, cisplatin, doxorubicin, and cyclophosphamide (FCAP) in 32 patients. Intensification after LOMAC was cyclophosphamide and thiotepa (CyTepa) with ASCR, and after FCAP it was cyclophosphamide, thiotepa, and carmustine (BCNU) in all but eight patients who received CyTepa. RESULTS Median survival from study entry for the entire group was 13.3 months. Median time to progression from reinfusion for the 45 patients who underwent intensification was 7.5 months. After LOMAC and intensification, there were 12 complete responses (CR) (nine partial responses [PRs] after induction converted to CRs). Responses after FCAP and intensification were eight CRs (two PRs after induction converted to CRs). Median time to treatment failure from reinfusion was 5.4 months for LOMAC and intensification, and was 10.5 months for FCAP and intensification. Median survival from study entry was 15.1 months for all 27 LOMAC patients and 9.3 months for all 32 FCAP patients. Median time to treatment failure from reinfusion for 11 patients who were CRs at intensification has not been reached and is more than 13 months compared with a median of 5.5 months for the 23 patients in partial remission at intensification. CONCLUSIONS High-dose intensification therapy has led to increased CR rates in metastatic breast cancer. The role of such therapy in the treatment of stage IV breast cancer requires further refinement.

The role of gallium-67 in the clinical evaluation of cancer.

This review is based primarily on historic data, and it examines the indications for and limitations of gallium-67 scanning in the evaluation of patients with neoplasms. The use of gallium-67 scans is discussed according to tumor type, and data from the most representative and comprehensive studies are included. The results described, some of which were obtained primarily with older imaging techniques, should be regarded as representing the minimum that can be expected from application of this imaging procedure.

High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer.

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.

Survival of patients with localized histiocytic lymphoma

Twenty of 65 patients with diffuse histiocytic lymphoma were identified by staging laparotomy as being in pathologic stages (PS) I, IE, II, and IIE. Six of the 20 patients were treated with total nodal, 10 with extended mantle, and four with involved‐field radiotherapy. The survival rate and relapse‐free survival at five years were 71% and 78%, respectively. All relapses occurred within the first year and were confined to patients with PS II disease and four or more sites of involvement. Accurate pathologic staging identifies patients who are potentially curable with radiotherapy. Further studies are required to determine the treatment necessary to achieve cure in PS II patients with more than four sites of involvement.

Diffuse histiocytic lymphoma with sclerosis: A clinicopathologic entity frequently causing superior venacaval obstruction

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to mega‐voltage radiotherapy alone and relatively resistant to combination chemotherapy.

Bone Marrow: Structure and Function

This is a well-written, up-to-date, concise text of bone marrow morphology (structure) and physiology (function). In 14 concise chapters, the authors review bone marrow phylogeny, ontogeny, structure, marrow circulation, marrow-blood barrier, marrow volume, population of cells, granulocyte production, erythropoiesis, thrombopoiesis, lymphopoiesis, stem cell compartments, and the role of stem cells. The text is authoritative and the references are up-to-date. The chapter on historic perspectives is a delight to read. One can learn how the bone marrows function was finally deduced. My only criticism is that the references should be listed on a chapter-to-chapter basis, rather than all together. Hematologists and physicians in postgraduate training programs in hematology will find this textbook a valuable addition to their libraries.

High-Dose Versus Standard Chemotherapy in Metastatic Breast Cancer: Comparison of Cancer and Leukemia Group B Trials With Data From the Autologous Blood and Marrow Transplant Registry

PURPOSE To assess survival of patients with metastatic breast cancer treated with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC). PATIENTS AND METHODS SDC in four Cancer and Leukemia Group B (CALGB) trials was compared with hematopoietic stem-cell support in patients from the Autologous Blood and Marrow Transplant Registry. Cox proportional hazard regression incorporated potentially confounding effects. A total of 1,509 women were enrolled onto CALGB trials, and 1,188 women received HDC. No significant survival differences existed by CALGB trial or HDC regimen. Consideration was restricted to candidates for both SDC and HDC. The resulting sample included 635 SDC and 441 HDC patients. The outcome of interest was overall survival. RESULTS The HDC group displayed better performance status. The SDC group had slightly better survival in first year after treatment. The HDC group had lower hazard of death from years 1 to 4 and had somewhat higher probability of 5-year survival (adjusted probabilities [95% confidence intervals], 23% [17% to 29%] v 15% [11% to 19%], P =.03). CONCLUSION After controlling for known prognostic factors in this nonrandomized analysis of two large independent data sets, women receiving HDC versus SDC for metastatic breast cancer have a similar short-term probability of survival, and might have a modestly higher long-term probability of survival.

A COMPARISON OF HLA-IDENTICAL SIBLING ALLOGENEIC VERSUS AUTOLOGOUS TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA: A REPORT FROM THE CIBMTR

We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P < .001), treatment failure (RR 2.06, 95% CI, 1.54-2.75, P < .001), and mortality (RR 2.75, 95% CI, 2.03-3.72, P < .001). Risk of disease progression was similar in the 2 groups (RR 1.12, 95% CI, 0.73-1.72, P = .59). In fact, for 1-year survivors, no significant differences were observed for TRM, progression, progression-free (PFS) or overall survival (OS). Increased risks of TRM and mortality were associated with older age (>50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT.

A phase I-II study of bialkylator chemotherapy, high-dose thiotepa, and cyclophosphamide with autologous bone marrow reinfusion in patients with advanced cancer.

Twenty patients with disseminated cancer both untreated and previously treated received bialkylator chemotherapy, thiotepa, and cyclophosphamide and reinfusion of cryopreserved autologous bone marrow (ABMR). The cyclophosphamide dose was constant at 7.5 g/m2 over three days, while thiotepa was started at 1.8 mg/kg for three days in escalating dose by a modified Fibonacci schema to 7 mg/kg. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets/microL was 18 and 27 days, respectively. Four patients died as a consequence of severe, overwhelming infections or progressive disease during their period of aplasia. Of the 18 evaluable patients, a complete response (CR) was achieved in three patients and a partial response (PR) in ten patients for an overall response rate of 72%. The median duration of response was 14 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, stomatitis, skin rash, and cardiomyopathy. The maximum tolerated dose (MTD) of thiotepa was 700 mg/m2 or 6 mg/kg for three doses. Although there are substantial toxicities associated with this regimen, high-dose thiotepa and cyclophosphamide produce high response rates in patients with disseminated cancer.