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Biomedical subjects

S N Wolff

Publications and source records attributed to S N Wolff.

At least 37 records · Page 2Linked to original sources
PubMed1997

Recurrent Hodgkin's disease after bone marrow transplantation.

Histologic features of recurrent Hodgkin's disease (HD) after conventional therapy are well known, but few studies describe HD after bone marrow transplantation (BMT). Histologic material from 63 patients who underwent BMT performed to treat recurrent nodular sclerosing HD (NSHD) between 1985 and 1994 was examined; 13 of the 63 patients had histologically proved recurrent disease after BMT. Histologic material and clinical findings from the original diagnostic biopsy specimen and pre-BMT and post-BMT specimens were available from our study population of eight patients (five male, three female; age range, 16 to 38 years; median age, 27.5 years). Seven patients had recurrent NSHD after BMT; sites of recurrence included lymph nodes only (four patients), and lymph nodes and lung, lung and liver, and lung only (one patient each). In one patient, a high-grade non-Hodgkin's B-cell lymphoma developed in the large intestine 5 years after BMT. In another, disease progressed from grade 1 in the original biopsy specimen to grade 2 in both the pre-BMT and post-BMT recurrent HD biopsy specimens. Post-BMT biopsy specimens of recurrent HD with lung involvement revealed a substantial increase in sclerosis and fibroblastic features. Paraffin immunoperoxidase studies in seven patients demonstrated substantial change in phenotype of Reed-Stemberg cell variants in only one post-BMT recurrent HD specimen, which showed a +2 reaction with CD30 (Ki-1). No substantial differences in the reactive component were noted between the original biopsy specimen and pre-BMT and post-BMT specimens of recurrent disease. In summary, histologic findings of post-BMT recurrent NSHD do not differ significantly from those of the original diagnostic biopsy or pre-BMT recurrent HD specimens. The lung is the most common site of extranodal post-BMT recurrence. In one patient, high-grade non-Hodgkin's B-cell lymphoma developed after BMT performed to treat recurrent HD.

Adolescent↗
PubMed1997

Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.

PURPOSE: Recipients of allogeneic bone marrow transplants (BMTs) who have relapsed may attain complete remissions when treated with transfusions of leukocytes obtained from the original bone marrow donor. We performed a retrospective study to characterize better this new treatment modality. PATIENTS AND METHODS: We surveyed 25 North American BMT programs regarding their use of donor leukocyte infusions (DLI). Detailed forms were used to gather data regarding the original BMT, relapse, DLI, response to DLI, complications of DLI, and long-term follow-up evaluation. Reports of 140 patients were thus available for analysis. RESULTS: Complete responses were observed in 60% (95% confidence interval [CI], 51.9% to 68.1%) of chronic myelogenous leukemia (CML) patients who received DLI and did not receive pre-DLI chemotherapy; response rates were higher in patients with cytogenetic and chronic-phase relapse (75.7%; 95% CI, 68.2% to 83.2%) than in patients with accelerated-phase (33.3%; 95% CI, 19.7% to 46.9%) or blastic-phase (16.7%; 95% CI, 1.9% to 31.9%) relapse. The actuarial probability of remaining in complete remission at 2 years was 89.6%. Complete remission rates in acute myelogenous leukemia (AML) (n = 39) and acute lymphocytic leukemia (ALL) (n = 11) patients who had not received pre-DLI chemotherapy were 15.4% (95% CI, 9.6% to 21.2%) and 18.2% (95% CI, 6.6% to 29.8%), respectively. Complete remissions were also observed in two of four assessable myeloma patients and two of five assessable myelodysplasia patients. Complications of DLI included acute graft-versus-host disease (GVHD) (60%; 95% CI, 51.4% to 68.6%), chronic GVHD (60.7%; 95% CI, 50.3% to 71.1%), and pancytopenia (18.6%; 95% CI, 12.2% to 25.0%). Pre-DLI characteristics predictive of complete response in CML patients were post-BMT chronic GVHD, pre-DLI disease status of chronic phase, and time interval between BMT to DLI less than 2 years. Acute and chronic GVHD post-DLI were highly correlated with disease response (P < .00001). CONCLUSION: DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response.

Actuarial Analysis↗
PubMed1997

The use of conventional salvage chemotherapy before dose-intensive cytotoxic therapy and autologous transplantation for aggressive-histology lymphoma: a case for re-evaluation.

The use of CSCT to judge suitability for DIT and AHSCT in patients with aggressive-histology lymphoma who recur after primary chemotherapy is a widespread practice that excludes many NHL patients from this potentially curative therapy. Surprisingly, little direct evidence exists to suggest that CSCT used in this way is a useful strategy. On the other hand, it is clear that many of these patients undergoing DIT and AHSCT will not be cured using any currently available strategy or technique, and a method to identify such patients would be most helpful. CSCT may or may not be the best way to do so. This is an important question, but currently there are insufficient data to give us a definitive answer. Clinical trials are needed to resolve the issue. If the utility of CSCT is not validated, it should be abandoned. If it is validated, however, we may begin to address ways in which CSCT may be given more effectively.

Antineoplastic Agents↗
PubMed1996

Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia.

The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein-negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Nocardial infections in bone marrow transplant recipients.

Infections caused by Nocardia species have been infrequently described in bone marrow transplant (BMT) recipients. We reviewed six cases of nocardiosis occurring in our population of BMT recipients and the four cases previously reported in the literature. The rate of nocardial infection at our institution was 0.2% (1 of 554) among autologous BMT recipients and 1.7% (5 of 302) among allogeneic BMT recipients (odds ratio, 9.3 [95% confidence interval, 1.1-80.1]; P = .046). All 10 patients had received immunosuppressive medications, and all but one allogeneic BMT recipient had acute or chronic graft-vs.-host disease (GVHD). Four patients had extensive exposure to soil or dust before nocardiosis developed. Seventy percent of the patients died, but death was less often due to progressive nocardial infection than to complications of GVHD and associated invasive infection with Aspergillus species. Three patients had nocardiosis despite receiving prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) on an intermittent basis two or three times a week. These data show that nocardial infection is an important if infrequent complication of bone marrow transplantation and is associated with a high rate of invasive fungal infection. TMP-SMZ prophylaxis given intermittently does not reliably protect against infection.

Adult↗
PubMed1996

High-dose etoposide, cyclophosphamide and total body irradiation with allogeneic bone marrow transplantation for resistant acute myeloid leukemia: a study by the North American Marrow Transplant Group.

We evaluated the toxicity and efficacy of high-dose etoposide, cyclophosphamide and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) for patients with resistant, acute myeloid leukemia (AML). Between 9/84 and 11/92 we treated 70 patients with etoposide (900-1800 mg/m2), cyclophosphamide (120-180 mg/kg) and TBI (1000-1200 cGy) followed by allogeneic BMT from histocompatible siblings. Forty patients were in untreated first relapse. Median time from diagnosis to transplant was 10 months. Toxicity was similar to that observed with cyclophosphamide/TBI with the median duration of neutropenia (ANC < 500/microliters) being 19 days (range 10-27) and the median duration of thrombocytopenia being 23 days (range 13-173). Twenty-three patients remain in continuous complete remission at a median of 56 months after transplant (range 36-132 months). Probabilities of disease-free survival, persistent/recurrent disease and transplant related mortality are .32, .47, and .37 respectively. Multivariate analysis indicated that grade > or = 2 acute graft-vs-host disease and transplant in untreated first relapse were associated with increased DFS due to reduced relapse risk. We conclude that high-dose etoposide with cyclophosphamide and TBI followed by allogeneic BMT is effective therapy for resistant AML, producing durable remission in approximately one-third of those treated. Disease persistence or recurrence was the major cause of treatment failure. Further improvement in DFS following allogeneic BMT for resistant AML might be achieved by using less intensive GVHD prophylaxis or through infusion of donor peripheral blood cells in patients who fail to develop significant acute GVHD.

Acute Disease↗
PubMed1996

Etoposide and mitoxantrone as a second cycle of consolidation therapy following high dose cytosine arabinoside and daunorubicin in patients with acute non-lymphocytic leukemia in remission: a pilot study.

High dose cytosine arabinoside (ARA-C) has produced long term relapse free survival in 26% to 49% of patients when used as consolidation therapy of acute non-lymphocytic leukemia (ANLL) in first remission. However, the optimal consolidation regimen has not been defined. In this pilot study we attempted to confirm and extend our previous studies of high dose consolidation therapy by administering two cycles of consolidation chemotherapy to patients with ANLL in first remission. The first cycle was high dose ARA-C 3 gm/m2 over 1 hour every 12 hours for 12 doses followed by daunorubicin 45 mg/m2/day for three days. The second cycle was etoposide 75 mg/m2/day for 10 days and mitoxantrone 12 mg/m2/day for three days. Twenty-three patients received high dose consolidation chemotherapy, 13 of whom received the proposed two cycles. The major reason for not receiving the planned second consolidation cycle was life threatening toxicity, primarily fungal infection, during the first consolidation cycle. By actuarial estimate, 46% of patients receiving consolidation chemotherapy were projected to be relapse free at 36 months. There were no deaths during consolidation. Survival was not improved in patients receiving etoposide and mitoxantrone as the second cycle of consolidation therapy as compared to patients receiving only one cycle of consolidation therapy.

Adult↗
PubMed1995

High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group.

Relapse is a major cause of treatment failure following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). To reduce the risk of relapse following BMT for patients with hematologic malignancy, our group developed a novel preparative regimen which combines high-dose etoposide with cyclophosphamide and total body irradiation (VPCyTBI). We now report the outcome of therapy with VPCyTBI followed by allogeneic BMT for 40 patients with AML in untreated first relapse. With the exception of increased stomatitis, the toxicity of this regimen was similar to that reported by others for CyTBI. Forty-four months after transplant the actuarial probabilities of disease-free survival (DFS), persistent or recurrent leukemia, and transplant related mortality were .29, .44, and .47 respectively. DFS was improved (P < .01) and risk of persistent or recurrent leukemia reduced (P = .005) among patients with significant (grade > or = 2) acute GVHD. Patients with 30% or more blasts on pre-BMT bone marrow examination were not at increased risk for persistent or recurrent leukemia. We conclude that VPCyTBI with allogeneic BMT is effective therapy for AML in untreated first relapse and that a randomized trial comparing this regimen with CyTBI is warranted.

Actuarial Analysis↗
PubMed1995

Seroepidemiology of Helicobacter pylori infection in heart transplant recipients.

We analyzed serum samples obtained from 100 heart transplant recipients before and after transplantation for the presence of IgG antibodies to Helicobacter pylori. Enzyme-linked immunosorbent assay revealed that 35 patients were seropositive before the procedure. Seropositive patients were older than seronegative patients, but the two groups did not differ in terms of cardiac diagnosis, gender, survival, or the number of admissions or rejection episodes. In addition, seropositive patients did not have more-frequent episodes of gastritis, ulcer disease, or gastrointestinal bleeding. Over a mean serological follow-up of 3.4 years, only one of 65 seronegative patients seroconverted. Of the 35 seropositive patients, 14 became seronegative for H. pylori a median of 194 days (range, 47-2,657 days) after transplantation. Seroreverters, as compared with serofast patients, had received more intravenous and total antibiotics during follow-up (P = .01), were more likely to have received a combination of antibiotics active against H. pylori (P < .025), and had received more antirejection treatment (P = .01). The incidence of H. pylori infection is not increased after heart transplantation, and many seropositive patients serorevert after transplantation when antibacterial and immunosuppressive agents are administered.

Adult↗
PubMed1995

T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.

PURPOSE: Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS: Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS: The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION: TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.

Adolescent↗
PubMed1995

Graft-versus-host-disease prophylaxis for matched unrelated donor bone marrow transplantation: comparison between cyclosporine-methotrexate and cyclosporine-methotrexate-methylprednisolone.

We performed a sequential study comparing two regimens, cyclosporine-methotrexate (CsA-MTX) and cyclosporine-methotrexate-methylprednisolone (CsA-MTX-MP) for graft-versus-host disease (GVHD) prophylaxis in patients undergoing matched unrelated donor bone marrow transplantation (MUD BMT). Study end-points were the development of GVHD, various infectious complications and survival. Twenty nine patients with malignant hematologic disease without HLA-compatible family donors were treated between May 1990 and November 1993. All donors were volunteers from the National Marrow Donor Program (NMDP) serologically HLA-A-A, B and DR identical. MLC reactivity and high resolution DR DNA typing were not used to exclude donors. Sixteen patients received CsA-MTX and 13 patients received CsA-MTX-MP. CsA and MTX doses were the same in both groups: CsA 1.5 mg/kg i.v. over 2h every 12h beginning the day prior to transplant (day-1) and MTX 10 mg/m2 i.v. bolus on days +1, +3 and +6 with leucovorin on days +2, +4 and +7. MP was administered at a dose of 0.25 mg/kg i.v. every 12h beginning on day +7 and increased to 0.5 mg/kg on day +14. Beginning on day +35 MP and CsA were tapered 5% per week with targeted discontinuation at 6 months. Both groups were comparable for primary disease, preparative regimen, recipient age (median 33 VS 33 years), donor age (median 39 vs 39.5 years), donor-recipient sex, donor ABO mismatch and serologic CMV positivity. All patients received similar supportive care.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Ringed sideroblasts: a frequent observation after bone marrow transplantation.

Dyserythropoiesis after bone marrow transplantation is common, but the presence of ringed sideroblasts (RS) has not been evaluated fully. To examine for RS, a combined silver and Perls' Prussian blue stain, shown previously to be more sensitive for detecting RS than Perls' Prussian blue stain alone, was used on post-transplant marrow aspirate sections from 39 patients who received marrow transplants (allogeneic, 28; autologous, 11) for a variety of disorders. Marrow aspirate sections were available for comparison from 11 of these patients before any treatment as well as from five patients with normal marrows and normal peripheral blood cell counts. Aspirates were not performed on donor marrows. By the modified silver stain, RS were present in 34 (87%) patients whose marrows were sampled 0.5 to 39 (median, 1.5) months post-transplant including 10 of 11 patients with autologous transplants (no graft versus host disease prophylaxis). In contrast, seven of 36 (19%) of these marrows contained RS when stained with Perls' reaction alone. Only one of 11 pretransplant marrows and none of five normal marrows contained RS when stained by either method. These results demonstrate that RS are present in most post-transplant marrows even beyond the usual period of reconstitution (28 days), and this finding can be included among the features of dyserythropoiesis seen after transplantation. RS apparently are not related to pretransplant pathology or post-transplant therapy. This study also confirms previous observations that modified silver stains are more sensitive for detecting RS than Perls' Prussian blue stain.

Adolescent↗
PubMed1993

High-dose weekly intravenous immunoglobulin to prevent infections in patients undergoing autologous bone marrow transplantation or severe myelosuppressive therapy. A study of the American Bone Marrow Transplant Group.

OBJECTIVE: To determine whether intravenous immunoglobulin (IVIG) prevents severe infections during autologous bone marrow transplantation or equivalent high-dose myelosuppressive therapy. DESIGN: Randomized, stratified, nonblinded study. SETTING: Three tertiary care university hospitals. PATIENTS: One hundred seventy patients entered the study; 82 received IVIG and 88 were untreated controls. The study groups were similar for parameters capable of influencing the likelihood of infection. INTERVENTIONS: Intravenous immunoglobulin was given weekly at a dose of 500 mg/kg body weight from the initiation of cytotoxic therapy to the resolution of neutropenia. MEASUREMENTS: The development of bloodstream or other clinically proven infection, platelet use, and the development of alloimmunity to platelet transfusion. RESULTS: Clinical infection, bacteremia, and fungemia occurred in 43%, 35%, and 6% of the IVIG-treated patients and in 44%, 34%, and 9% of the control patients. Gram-positive bacteremia and gram-negative bacteremia occurred in 28% and 11% of the IVIG group and in 23% and 13% of the control group. Death due to infection occurred in 4.9% of IVIG recipients and in 2.3% of controls. None of these observations was statistically significant (P > 0.2). Survival to hospital discharge was achieved in 86.6% of the IVIG group and in 96.6% of the control group. The survival difference (10%; 95% CI, 1.7% to 18.3%; P = 0.02) was due to a higher incidence of regimen-related toxic death in the IVIG-treated group. CONCLUSIONS: The use of IVIG did not prevent infection. Fewer deaths occurred among controls due to a higher incidence of fatal hepatic veno-occlusive disease in patients receiving IVIG.

Adolescent↗
PubMed1993

Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy.

PURPOSE: Despite substantial advances in the treatment of aggressive non-Hodgkin's lymphoma, therapeutic results with conventional regimens remain poor in some subsets of patients. In an attempt to improve the prognosis of such patients we used an 8-week, multidrug chemotherapy regimen of high dose-intensity. PATIENTS AND METHODS: Between April 1986 and April 1991, 70 patients with advanced intermediate- or high-grade non-Hodgkin's lymphoma were treated. The median age was 41 years (range, 18 to 69). Fifty-one patients (73%) had stage IV disease; 37 (53%) were Shipp's category 3; 17 (24%) had small noncleaved-cell lymphoma; 35 (50%) had Eastern Cooperative Oncology Group (ECOG) performance status > or = 2; 24 (34%) had two or more extranodal sites involved; and 17 (24%) had bone marrow involvement. The 8-week regimen included cyclophosphamide, etoposide, doxorubicin, vincristine, bleomycin, methotrexate with leucovorin rescue, and prednisone. RESULTS: Sixty-two of 70 patients completed the regimen as planned. Fifty-seven patients (81%) obtained a complete response (CR) and the actuarial 5-year failure-free survival rate is 52%. Thirty-seven patients remain alive and disease-free a median of 35 months (range, 7 to 68) after therapy. Adverse prognostic factors included age more than 50 years, bone marrow involvement, and serum lactic dehydrogenase (LDH) more than 500 IU/L (normal range, 125 to 250). Myelosuppression was responsible for most of the treatment-related toxicity. Severe leukopenia (< 1,000/microL) occurred in all patients and lasted a median of 9 days. Seven patients (10%) died of myelosuppression-related complications; five of these patients were older than 60 years. CONCLUSION: This brief but intensive therapy was effective in treating poor-prognosis patients with non-Hodgkin's lymphoma. With this therapy, patients with small noncleaved-cell lymphoma or Shipp's category 3 disease had treatment outcome similar to the group as a whole. This therapy was not well tolerated by patients older than 60 years, and should not be given to this subgroup. Verification of these results in a randomized trial setting is indicated.

Adolescent↗
PubMed1991

Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma.

A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (greater than 300 IU/l), 43%; and bulky (greater than 10 cm) tumor masses, 30%. Thirty-three of 56 patients (59%) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 IV on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (less than 1000/microliters) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.

Adult↗
PubMed1991

A brief-duration combination chemotherapy for elderly patients with poor-prognosis non-Hodgkin's lymphoma.

Curative combination chemotherapy is available for many patients with aggressive non-Hodgkin's lymphoma (NHL); however, treatment of elderly patients with these regimens is difficult due to excessive toxicity. From 1983 to 1988 the authors treated 26 patients 65 years and older with aggressive NHL with a novel 8-week chemotherapy regimen containing bleomycin, etoposide, cyclophosphamide, doxorubicin, methotrexate with leucovorin, and prednisone (BECALM), designed to preserve dose intensity and minimize toxicity. Median age was 75 years. Histologic types included the following: 20 intermediate grade (16 large noncleaved cell; two large cleaved cell; one intermediate grade, unspecified); six high grade (four small noncleaved cell; one immunoblastic sarcoma B-cell; one high grade, unspecified). Twenty-one patients were Stage III or IV. Twenty-two of 26 patients had one or more of the following: tumor greater than 10 cm; multiple extranodal sites; lactate dehydrogenase (LDH) 400 IU/l or greater; small noncleaved cell histologic type. Chemotherapy consisted of bleomycin 20 U intravenously (IV) weeks 1 and 7; etoposide 75 mg/m2 IV every day x 3 days on week 4; cyclophosphamide 600 mg/m2 IV weeks 1, 4, 7; doxorubicin 40 mg/m2 IV weeks 1, 7; methotrexate 50 mg/m2 IV weeks 1, 2, 4, 5, 7, 8 with oral leucovorin rescue; prednisone 60 mg orally for 10 days on weeks 1, 4, 7. Eighteen patients completed the 8-week treatment course. There were 13 complete responses (CR); seven patients remain in continuous CR at a median follow-up of 37.5 months. There have been five relapses, including one late relapse; and one patient died of an intercurrent illness in CR. Overall and actual event-free survivals are 38% and 27%, respectively. The major toxicities were neutropenic fever and mucositis. There were four treatment-related deaths. The authors conclude that BECALM chemotherapy can be administered to elderly patients with aggressive NHL. Although neurotoxicity and cumulative toxicity from bleomycin and anthracycline are avoided, the regimen remains moderately toxic, particularly with respect to myelosuppression. Treatment results compare favorably with other reported regimens in this group of patients with multiple poor prognostic features.

Aged↗
PubMed1991

Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma.

Thirty-one patients were diagnosed by morphologic and immunophenotypic features as having primary Ki-1 anaplastic large-cell lymphoma (Ki-1 ALCL). the median age was 35 years (range, 4 months to 78 years); the male:female ratio was 18:13. B symptoms were observed in 13 patients. Peripheral adenopathy was present in 26 patients, while mediastinal adenopathy occurred in five. There was extranodal disease in 13 patients; the most common extranodal site was skin with seven affected. Seventeen patients had stage III/IV disease. Immunophenotypes were T cell in 24 patients and B cell in four patients; immunophenotype could not be determined in three patients. Cytogenetic abnormalities in chromosomes 2, 5, and 7 were detected in three patients. Although therapy was heterogeneous, the actuarial 2-year survival was 73%. Two-year disease-free survival was 39% for all patients; for stages I and II, it was 62% compared with 20% for stages III and IV (P = .001). Complete remission (CR) occurred in 21 of 23 patients receiving combination chemotherapy; however, nine relapses, including six of seven stage IV patients, occurred within 21 months of diagnosis. Preliminary observations suggest that Ki-1 ALCL may have a quiescent phase in the rare patient with only localized skin disease. However, the disease generally behaves as an intermediate- to high-grade lymphoma, and patients with Ki-1 ALCL should receive curative-intent combination chemotherapy.

Actuarial Analysis↗