Mixed outpatient-inpatient autologous stem cell transplant for multiple myeloma: A cost-saving initiative in a resource constrained environment.

Background Although administration of chemotherapy prior to autologous stem cell transplantation in the outpatient setting has been reported as safe and cost-effective, many limitations exist with previously reported methods of transitioning out of the hospital ward. Specifically, lack of a caregiver and distance from treatment facility are key factors particularly in rural settings. Given these limitations, not all institutions have transitioned the transplant process, or even portions of it, to the outpatient setting despite the known benefits. Methods To achieve financial benefit without compromising safety, a novel mixed outpatient-inpatient model was adopted at our institution. Eligible patients receive melphalan in the clinic the day prior to being admitted for peripheral blood stem cell re-infusion where they remain until recovery of myelosuppression. Results In the year since implementation, nineteen total patients received high-dose melphalan prior to autologous stem cell transplantation. Eighteen of these patients successfully received melphalan in the outpatient clinic with admission to the hospital on day zero for infusion of stem cells. No patient experienced any adverse event on the day or evening of chemotherapy or required early admission. The average estimated total reduction in cost per patient to the institution was over US$2,000. When comparing the cost of the chemotherapy drug, melphalan, from the year before and the year after implementation of the mixed model the total annual cost saving was approximately US$90,00 or 53% of the previous year's expenditure. Conclusions The implementation of this mixed outpatient-inpatient model was safe, feasible, and cost-effective.

Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions.

Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties to find donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD), and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase 1/2 trials at many centers. Preliminary data indicate that GVHD could be prevented with transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD.

Combined submyeloablative and myeloablative dose intense melphalan results in satisfactory responses with acceptable toxicity in patients with multiple myeloma.

We studied in patients with multiple myeloma (MM) the efficacy, cost-effectiveness, and toxicity of a strategy of submyeloablative doses of Mel and stem cell support in the ambulatory setting, followed by a standard myeloablative dose transplant. Patients with recently diagnosed symptomatic MM received dexamethazone to induce clinical response. Cytokine mobilized peripheral blood progenitor cells (PBPC) were split into 2 aliquots and cryopreserved. Patients then received Mel 100 mg/m(2) (Mel100) and infusion of the first PBPC aliquot in an ambulatory facility. Individuals received standard neutropenia prophylaxis and no growth factor support, but were seen regularly at the clinic until recovery. The cost of this step was calculated in a cohort of 23 patients where information for the expenditure was available. Six months later patients were conditioned in the hospital with Mel 200 mg/m(2) (Mel 200) followed by nfusion of the second aliquot. This study tested the cost, effectiveness, and the toxicity of out-patient-based transplantation, as well as the rate of response (complete remission [CR], very good partial remission [VGPR], partial remission [PR], and stable disease [SD]) and overall survival (OS) of this strategy. Twenty-six female and 16 male patients, with a median age of 53 years (range: 33-68 years) and median Salmon & Durie clinical disease stage III (range: II-III) were studied. The paraprotein was IgA in 17%, IgG in 52%, and light chains in 26%. The median harvested CD34(+) x 10(6) cells/kg was 12.03 (2.25-55.4). The median interval between the 2 transplant procedures was 239 (105-376) days. The median Karnofsky presentation score was 40%, but improved to 80% after the Mel 100 and was 90% following Mel 200. Subsequent to MEL 100 response was complete (CR) in 7 and it was VGPR in 9. Mel 100 grade 3-4 toxicity was mainly hematologic, but 15 (36%) required hospital admission for a median of 5 days. The median cost of MEL100 and corresponding supportive therapy was U.S. $2,142.35. In addition, the total median cost of those who needed admission to hospital was U.S. $6,042.78. Thus, pooling costs from patients who needed or did not need admissions the average cost of this strategy was U.S. $3,546.50 per patient. Among Mel 200 patients, except for hematologic toxicity, no patient had greater than grade 2 side effects. On completion of the program, 20 (48%) patients achieved CR, a further 14 (33%) had VGPR, whereas 6 had PR. At a median follow-up of 659 days there were 8 deaths, 1 (2%) was related to the treatment procedures and 6 from disease progression; thus, the 1000 days OS was 73%. Significant adverse factors included older age, lower presentation Hb, and lower Karnofsky %. Nonparametric testing confirmed that good performance scores and VGPR or CR were associated with more favorable outcome. Importantly, these satisfactory results were obtained in the absence of the new biologic cell modifiers. Mel 100 was well tolerated in the outpatient setting and the overall strategy seems to be effective in inducing durable responses with acceptable toxicity.

Biochemical markers and assessment of cardiotoxicity during preparative regimen and hematopoietic cell transplantation in acute leukemia.

INTRODUCTION: Cardiotoxicity is a relatively frequent and potentially serious complication of antitumor treatment. Anthracyclines and other high-dose chemotherapy represent the greatest risk. The aim of the study was to assess cardiotoxicity during preparative regimen (PR) and hematopoietic cell transplantation (HCT) in acute leukemia (AL) with biochemical markers - "N-terminal pro brain natriuretic peptide" (NT-proBNP), cardiac troponin T (cTnT) and creatine kinase MB (CK-MB mass). METHODS: Nineteen adult AL patients previously treated with anthracyclines--idarubicine, daunorubicine, mitoxantrone with standard doses for a cycle as 3 x 12 mg/m(2), 3 x 50 mg/m(2), 3 x 10 mg/m(2) accordingly were studied. PR consisted of high-dose cyclophosphamide (HD-C) in combination with busulphan or total body irradiation (TBI). Plasma NT-proBNP, cTnT and CK-MB mass concentrations were measured the day before PR, the day after PR, the day after HCT and 14 days after HCT. RESULTS: Before PR, mean plasma NT-proBNP value was 106.3+/-55.7 ng/l. After PR, it increased to 426.1+/-391.5 ng/l. After HCT, a further increase to 847.6+/-780.6 ng/l was observed. Fourteen days after HCT, the mean NT-proBNP was 330.8+/-236.8 ng/l. The differences were statistically significant in comparison with the baseline values (p<0.01). The NT-proBNP elevations were more pronounced in patients with cumulative doses (CD) of anthracyclines above 450 mg/m(2) (p<0.05), in patients with PR containing HD-C and TBI (p<0.05). In all patients, plasma cTnT and CK-MB mass concentrations remained unchangable during PR and HCT. CONCLUSION: Our results suggest that administration of PR and HCT is in most AL patients associated with acute neurohumoral activation (significant rise in NT-proBNP). Persistent NT-proBNP elevations, in our study in 12 (63.2%) patients, indicate subclinical cardiotoxicity (risk for development of heart failure) and require further follow-up. More pronounced NT-proBNP elevations in patients with higher CD of anthracyclines and in patients with PR containing combination of HD-C and TBI confirm that these therapeutic procedures seem to be more cardiotoxic and not very appropriate for patients with cumulation of risk factors for cardiotoxicity. Negative plasma cTnT and CK-MB mass concentrations show no detectable damage of cardiomyocyte structure during PR and HCT.

Breaking dogmata to help patients: non-myeloablative haematopoietic stem cell transplantation.

Various dogmata have been broken as a consequence of the evolution of knowledge in the area of allogeneic haematopoietic stem cell (HSC) transplantation. The following is now clear: for the successful engraftment of allogeneic HSC, bone marrow ablation of the recipient is not required; HSCs create their own space through graft-versus-host reactions; several malignancies can be eradicated by the graft-versus-tumour effect; HSC allografting can be conducted on an out-patient basis; HSC allografting can be done in aged or debilitated individuals; HSC allografting can be achieved without transfusion of blood products; and the costs of the allografting procedures can be substantially diminished. Despite the fact that HSC allografting with reduced intensity conditioning may be related to several disadvantages, such as mixed chimaerism and relapse of the malignancy, breaking these dogmata has resulted in availability of HSC allografting to a larger number of individuals worldwide, thus offering true curative therapeutic options to patients who otherwise would not qualify to be given these opportunities.