Near-complete Remission Research Articles

Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial

AbstractHigh-dose therapy is an effective standard treatment for multiple myeloma patients. Evidence that intermediate-dose therapy improves survival is limited. At diagnosis, about 70% of patients are older than 65. Intermediate-dose regimen is very well tolerated in older patients. In a multicenter study, 194 patients were randomized to receive at diagnosis either conventional chemotherapy (6 courses of oral melphalan and prednisone [MP]) or intermediate-dose therapy (2 courses of melphalan at 100 mg/m2 [MEL100]) with stem cell support. Response rate was higher after MEL100. Near-complete remission (nCR) was 6% after MP and 25% after MEL100 (P = .0002). At 3 years, MEL100 increased event-free survival (EFS) from 16% to 37% and overall survival (OS) from 62% to 77% (P < .001). Similar results were observed in patients aged 65 to 70: nCR was 8% after MP and 25% after MEL100 (P = .05); at 3 years, MEL100 improved EFS from 18% to 31% (P = .01) and OS from 58% to 73% (P = .01). Patients aged 65 to 70 had a median OS of 37.2 months (MP) versus 58 months (MEL100). Intermediate-dose melphalan improves response rate, EFS, and OS in myeloma patients, specifically in those aged 65 to 70. It constitutes a more effective first-line regimen than standard treatment for elderly patients.

Sternal Hump

A 16-year-old boy was admitted to our hospital because of a sternal mass and mediastinal enlargement noted on an x-ray film after thorax trauma. The mass had appeared 11 months earlier after physical exertion and had been interpreted as sternal dislocation. The patient reported no symptoms. Physical examination revealed a painless “sternal hump” without inflammatory signs and bilateral cervical lymphadenopathy. A magnetic resonance image showed an anterior mediastinal mass eroding the sternal manubrium. Fine-needle aspiration of the mass was nondiagnostic, but biopsy of a cervical node disclosed Hodgkin disease, nodular sclerosis type. After 3 cycles of chemotherapy, near-complete remission was achieved, and the mass disappeared. Onset of Hodgkin disease as a sternal mass is extremely unusual and usually associated with the nodular sclerosis type. The atypical onset and painless course of the lesion explain the important diagnostic delay in most reported cases.

High-dose therapy and immunomodulatory drugs in multiple myeloma

The principle of alkylating agent dose intensity, especially with melphalan-based tandem autotransplants, has been effective in increasing the rate of complete remission beyond 40% and effecting 10-year survivorship in about 40% of the three fourths of patients presenting without cytogenetic abnormalities (Total Therapy I). Further dose escalation and post-transplant consolidation therapy, as practiced with Total Therapy II, seems to further improve results in these patients, but not in those with chromosome 13 abnormalities or lactate dehydrogenase elevation. Phase III trials for post-transplant relapse indicate higher complete remission and near-complete remission rates among patients randomized to thalidomide added to dexamethasone versus dexamethasone alone. In a phase I/II study, thalidomide derivative CC-5013, with less sedative and neurotoxic effects, promoted responses in eight of 15 patients with post-transplant relapse, refractory to other salvage therapies, at dose levels of ≥ 25 mg daily. Based on a profound graft-vs-myeloma effect with allografts, mini-allotransplants were evaluated in 31 high-risk patients with cytogenetic abnormalities and prior autotransplants; all nine with responsive disease and only one prior autotransplant remain disease-free and alive. Such mini-allotransplants are now offered as consolidation after one standard autotransplant to patients with cytogenetic abnormalities. The systematic application of gene expression profiling attempts to classify multiple myeloma (MM) patients according to molecular features and to dissect the genetic basis for drug sensitivity or resistance. Given the availability of an expanding treatment armamentarium (eg, thalidomide, CC-5013, the proteasome inhibitor PS-341, farnesyltransferase inhibitors, IL-6 receptor antibody, endothelial receptor inhibitor), gene expression profiling is anticipated to help in the selection of agents with the greatest probability of activity toward individualized treatment. Careful scrutiny of gene expression will also help in the identification of unrecognized targets for therapeutic intervention. Semin Oncol 29 (suppl 17):26-33. Copyright 2002, Elsevier Science (USA). All rights reserved.

High-dose therapy and immunomodulatory drugs in multiple myeloma.

The principle of alkylating agent dose intensity, especially with melphalan-based tandem autotransplants, has been effective in increasing the rate of complete remission beyond 40% and effecting 10-year survivorship in about 40% of the three fourths of patients presenting without cytogenetic abnormalities (Total Therapy I). Further dose escalation and post-transplant consolidation therapy, as practiced with Total Therapy II, seems to further improve results in these patients, but not in those with chromosome 13 abnormalities or lactate dehydrogenase elevation. Phase III trials for post-transplant relapse indicate higher complete remission and near-complete remission rates among patients randomized to thalidomide added to dexamethasone versus dexamethasone alone. In a phase I/II study, thalidomide derivative CC-5013, with less sedative and neurotoxic effects, promoted responses in eight of 15 patients with post-transplant relapse, refractory to other salvage therapies, at dose levels of > or = 25 mg daily. Based on a profound graft-vs-myeloma effect with allografts, mini-allotransplants were evaluated in 31 high-risk patients with cytogenetic abnormalities and prior autotransplants; all nine with responsive disease and only one prior autotransplant remain disease-free and alive. Such mini-allotransplants are now offered as consolidation after one standard autotransplant to patients with cytogenetic abnormalities. The systematic application of gene expression profiling attempts to classify multiple myeloma (MM) patients according to molecular features and to dissect the genetic basis for drug sensitivity or resistance. Given the availability of an expanding treatment armamentarium (eg, thalidomide, CC-5013, the proteasome inhibitor PS-341, farnesyltransferase inhibitors, IL-6 receptor antibody, endothelial receptor inhibitor), gene expression profiling is anticipated to help in the selection of agents with the greatest probability of activity toward individualized treatment. Careful scrutiny of gene expression will also help in the identification of unrecognized targets for therapeutic intervention.

The role of chemotherapy in the nonsurgical management of malignant neuroendocrine tumours.

1993). The initial management of NET comprises surgical excision of the primary tumour (aimed at reducing as much as possible of the tumour mass); additionally, in patients who are not cured by surgery alone, medical therapy is used for the control of symptoms and humoral syndromes with agents such as somatostatin analogues and/or a-interferon. Specific therapy with radiopharmaceuticals using radio-labelled substances such as meta-iodobenzylguanidine (MIBG) or somatostatin analogues appears promising for some tumours which show diagnostic uptake, and is the first-line systemic management for sensitive cases. Hepatic artery ligation and/or chemoembolization is also used in patients with excessive hepatic tumour load and uncontrollable symptoms. The control of tumour growth with chemotherapeutic agents is currently mainly reserved for patients with recurrent and/or progressive disease and where other therapeutic modalities have failed. Chemotherapy may be particularly helpful for selected cases of advanced NET, especially pancreatic or poorly differentiated NET. This review deals with the general role of chemotherapy in the management of malignant NET, its integration with other modes of therapy, and the specific protocols which have been used. Histological classification and differentiation of NET

Recurrent Priapism During Treatment With Clozapine and Olanzapine

Back to table of contents Previous article Next article Letter to the EditorFull AccessRecurrent Priapism During Treatment With Clozapine and OlanzapineMICHAEL T. COMPTON, M.D., AIDA SALDIVIA, M.D., and SALLY A. BERRY, M.D., PH.D., MICHAEL T. COMPTONSearch for more papers by this author, M.D., AIDA SALDIVIASearch for more papers by this author, M.D., and SALLY A. BERRYSearch for more papers by this author, M.D., PH.D., Atlanta, Ga.Published Online:1 Apr 2000AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We report a case of priapism after the administration of olanzapine in a patient who on two previous occasions had had priapism that was associated with clozapine treatment. The first case of priapism associated with atypical antipsychotics was reported in 1992 and involved clozapine (1). Subsequently, at least five other reports of clozapine-associated priapism have appeared in the literature. The first reported cases of priapism after the administration of olanzapine were published in 1998 (2, 3). Many medications have been associated with priapism, which is thought to be related to α-adrenergic blockade. Olanzapine has a pharmacological profile similar to that of clozapine, with a high affinity for dopamine D1, D2, and D4, serotonin (5-HT) 5-HT2A, 5-HT2C, and 5-HT3, muscarinic, α1-adrenergic, and histamine H1 receptors. This medication is increasingly used because of its proven antipsychotic activity and favorable side effect profile.Mr. A was a 43-year-old man diagnosed with schizoaffective disorder of the bipolar type. He began clozapine therapy for refractory psychosis, which resulted in near-complete remission of his psychotic symptoms. However, he later experienced two episodes of prolonged painful erection, which lasted approximately 12.0 and 13.5 hours. Mr. A’s clozapine treatment was discontinued, and during the next 2 years his condition was stabilized with olanzapine, divalproex, and thiothixene. His medical records indicated that an adequate response was not achieved with the combination of divalproex and olanzapine or divalproex and thiothixene.Mr. A was then hospitalized for exacerbation of his psychosis. He had been noncompliant with his psychotropic treatment for 3 weeks before admission. At admission, his treatment regimen was reinitiated, as previously prescribed, with 25 mg/day of olanzapine, 1000 mg/day of divalproex, and 5 mg/day of thiothixene. The next morning he awoke with a painful erection. With conservative drug management, the priapistic episode began to remit after 5 hours. Mr. A’s penis returned to normal flaccidity after 8 to 10 hours. His dose of olanzapine was discontinued, and he was stabilized with 25 mg/day of thiothixene. This adverse event was reported to the manufacturer and the Food and Drug Administration.This case represents the third published report of priapism associated with the administration of olanzapine of which we are aware. Although thiothixene has been reported to cause priapism, as have many other conventional antipsychotics, the patient did not experience an episode during his stable period with an increased dose of thiothixene. None of his other medications (divalproex, gemfibrozil, or glyburide) have been reported to cause this adverse event. His three priapistic episodes may indicate a sensitivity to the shared pharmacologic properties of clozapine and olanzapine. His most recent priapism was most likely due to the α-adrenergic-blocking capacity of olanzapine. We believe this case may be of heuristic value and caution clinicians who prescribe olanzapine to men with a history of priapism.

Carcinoma of the uterine cervix metastatic to behind the zygomatic arch: A case report

Purpose: We propose to present a novel case of a genital malignancy metastatic to the head and neck. Carcinoma of the uterine cervix is the third most frequent malignancy of the female genital tract. Early detection and improved radiation and surgical techniques have resulted in better control of the pelvic tumor and a greater incidence of distant metastasis. Metastases to the soft tissue of the head and neck region have not been reported. Methods: We present the first known case of a 35-year-old woman with cancer of the uterine cervix who presented with metastasis to the soft tissue behind the zygomatic arch. Results: The patient received radiation therapy to the zygomatic region and cisplatin therapy with a near-complete remission. Conclusion: This case shows that not all squamous cell cancers detected above the clavicles are from a thoracic or a head and neck primary tumor. The atypical location should alert the physician to suspect distant metastasis, rather than locoregional disease.

Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients.

We review the efficacy, tolerability and safety of low-dose thalidomide in the treatment of refractory disfiguring rash in 16 patients with cutaneous manifestations of lupus. Rashes, which included discoid lupus erythematosus (DLE), subacute cutaneous lupus (SCLE), photosensitive malar rash and non-specific chronic erythema, were diagnosed on clinical grounds, supported by skin biopsy in 11/16 patients. Using starting doses of 50-100 mg/day, 7/16 (44%) patients gained complete or near-complete remission of skin disease and 6/16 (37%) partial remission. Three out of 16 patients failed to respond. Maximum benefit was achieved within 16 weeks in all patients. Doses of 25-50 mg/day were effective in maintaining response. Rapid relapse occurred in 6/8 (75%) patients following drug withdrawal, but the response to thalidomide in those requiring repeat courses appeared to be maintained. There was no detectable improvement in systemic disease. One patient developed symptoms of mild peripheral neuropathy which resolved on drug withdrawal. Our experience suggests that thalidomide is effective in the treatment of severe skin manifestations of lupus refractory to other treatment and can be used safely in specialist rheumatological practice.

Steroid-resistant nephrotic focal segmental glomerulosclerosis: a treatable disease.

If not aggressively treated, oral steroid-resistant (SRst) nephrotic focal segmental glomerulosclerosis (FSGS) is likely to progress to end-stage renal failure. Three observations challenge the conclusion of the International Study of Kidney Diseases in Children (ISKDC) that SRst FSGS is unresponsive to further immunosuppression: (1) The ISKDC definitions of response and relapse, which fit the patterns in minimal change disease, precluded appropriate recognition of partial or gradual responses. (2) In two ISKDC studies, a small number of children with FSGS in one case, and the use of a year of alternate-day prednisone as a control in the other, may have obscured the effects of cyclophosphamide. (3) Recent studies of more aggressive therapies have provided strong evidence of benefit. High-dose methylprednisolone infusion therapy, with alternate-day prednisone alone or with alternate-day prednisone plus an alkylating agent (the M-P/ triple therapy protocol) has achieved sustained, complete remissions with stable renal function in 66% of children with SRst FSGS, and near-complete resolution of proteinuria in another 9%. Cyclosporine (CsA) plus alternate-day prednisone has produced complete or near-complete remissions in 35% of similar cases. Whether or not controlled studies will confirm the apparently greater efficacy of the M-P/triple therapy protocol, the favorable outcomes with both the M-P and the CsA regimens support the conclusion that a conservative approach to SRst FSGS is no longer appropriate.

Response to thymectomy in South Indian patients with myasthenia gravis.

The rate of remission among patients with myasthenia gravis (MG) following thymectomy and the predictors of the outcome have revealed vast variation in studies from different geographic regions raising suspicion about the influence of ethnic factors. We retrospectively evaluated the outcome of 71 South Indian MG patients who were thymectomized between 1987 through 1993 and analyzed the relationship between clinical and histopathological features and postthymectomy outcome. The clinical severity of the disease did not differ between the 29 patients with and 42 patients without a thymoma. Seventynine percent of our patients responded favourably to thymectomy; without additional immunosupression therapy, 52% achieved a near-complete remission. An younger age and milder disease correlated with a good outcome. Patients with thymoma responded as favourably as those without a thymoma. The postthymectomy response of South Indian MG patients in general did not differ from that of Western and Oriental patients.

Phase I Trial of an Anti-CD19 Deglycosylated Ricin A Chain Immunotoxin in Non-Hodgkinʼs Lymphoma

In a phase I trial, eight patients with non-Hodgkin's B-cell lymphoma received mouse IgG1k monoclonal antibody HD37 specific for CD19 conjugated to deglycosylated ricin A chain (dgA) administered in four doses at 4-h intervals with total doses ranging from 4-12 mg/m2. This schedule generated serum levels of immunotoxin which were sustained over 36 h. The plasma half-life of HD37-dgA was 17 +/- 4 (SD) h. The HD37-dgA conjugate was stable in vivo as demonstrated by serum levels of HD37-dgA conjugate comparable to those of total HD37 antibody. Peak serum levels attained after the fourth dose ranged from 0.36 to 5.63 micrograms/ml. Two of seven evaluable patients developed modest human anti-immunotoxin antibody responses. Toxicity in patients 1-7 consisted of dose-dependent capillary leak syndrome with hypoalbuminemia, orthostatic hypotension, and weight gain. Patient 8 died on day 8 with severe capillary leak, bronchopneumonia, and rhabdomyolysis. All patients had progressive disease at 4 weeks except patient 8, who exhibited a near-complete remission before his death. This intensive schedule appears to produce inordinate toxicity with a maximal tolerated total dose of 8 mg/m2.

Modeling the Client's World Through Brief Solution-Focused Therapy

The shift to a managed care philosophy means that clients with psychiatric needs are likely to have both fewer and briefer inpatient hospitalizations. Identification of focused goals and measurable outcomes may not translate easily into inpatient programs that have been more process oriented or have based definitions of improvement on complete or near-complete remission of the admission diagnosis. In the context of these shifts, nursing's focus on maintaining a safe environment, developing a therapeutic relationship, providing information, and valuing holistic and individualized care may be lost in programs that treat all clients in the same "packaged" programs. This article describes the philosophical assumptions that underlie the brief inpatient program. The next article in this issue describes how solution-focused therapeutic modalities are used in the continuum of care.

Carcinoma-associated hemolytic-uremic syndrome: a complication of mitomycin C chemotherapy.

A thrombotic microangiopathy resembling the hemolytic uremic syndrome was diagnosed in 12 patients with adenocarcinoma, in whom the tumor was in complete or near-complete remission after treatment with mitomycin C-containing drug regimens. Microangiopathic hemolytic anemia, thrombocytopenia, and renal failure were initially present in all cases. All patients eventually developed pulmonary edema and systemic arterial hypertension, and three experienced neurologic complications. Blood transfusions exacerbated the syndrome in nine patients. High titers of platelet-aggregating plasma immune complexes were present in all six cases in which they were measured. The constituent antibody of each complex failed to react with mitomycin C antigen preparations, whereas in vitro reactivity to endodermally derived neoplasms was demonstrated. Plasmapheresis was associated with amelioration of the syndrome in only one patient. In patients receiving mitomycin C chemotherapy, the development of anemia and thrombocytopenia or azotemia may represent the initial manifestations of this newly defined thrombotic microangiopathy. A consistently effective form of management of this syndrome has not as yet been defined.

Hepatic glomerulonephritis. Role of hepatitis B surface antigen (HBsAg).

A possible role of HBsAg in hepatic glomerulonephritis was evaluated in kidney specimens from 104 patients with various diseases. Huang's method using formalin-fixed and paraffin-embedded sections was applied to the kidney from 65 cases. Only 4 (3.8%) with liver cirrhosis had glomerular HBsAg deposition; 3 on frozen and one on paraffin sections. In one case of crescentic glomerulonephritis, HBsAg appeared to have had a pathogenetic role with glomerular immunofluorescence dominant for IgM, less intense IgG and negative IgA. The glomerular HBsAg in the remaining 3 patients with hepatic IgA glomerulonephritis was likely to be concomitant or superimposed. One of them had a nephrotic syndrome for which corticosteroid treatment was given, resulting in a near-complete remission and disappearance of HBsAg in the glomeruli, but the glomerular immunohistology was unaffected by the treatment. The present findings suggest that HBsAg has only a minor role.