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Options for treatment of elderly patients with multiple myeloma have expanded substantially following the development of immunomodulatory drugs (IMiD), proteasome inhibitors and with enhancement in safety of high-dose therapy and autologous stem cell transplant (HDT + ASCT). The recognition of biological heterogeneity among elderly patients has made delivery of therapy more challenging. An individualised approach to treatment selection is recommended in an era in which highly efficacious treatment options are available for transplant-ineligible patients. Here, we summarise recommendations for patients who are considered unsuitable for HDT + ASCT, including pretreatment considerations, and induction, maintenance and supportive care therapies., (© 2015 Royal Australasian College of Physicians.)

Introduction: Patients with Hodgkin's Lymphoma (HL) who relapse or progress after primary therapy and subsequent high dose chemotherapy with autologous stem cell transplantation (ASCT) cannot be cured with conventional treatment. We combined thalidomide (THAL), an agent with anti-angiogenic and immunomodulatory properties, with vinblastine, which is active after ASCT, to determine the objective response rate, improvement in B symptoms and toxicity in patients with refractory HD., Methods: Patients were eligible if they HD that progressed after chemotherapy and ASCT or had declined or were ineligible for curative therapy. Treatment consisted of THAL 200 mg orally given daily. After 2 weeks, VBL 6 mg IV was given weekly x 6 doses on an eight-week cycle. Response and toxicity assessment occurred following each cycle., Results: Eleven patients were enrolled, 1 progressed within 6 days of study enrollment and was subsequently treated with alternative palliative therapy and thus 11 patients are response evaluable and 10 are evaluable for toxicity., Patient Characteristics: relapsed after ASCT: 7; median number of prior chemotherapy regimens: 3 (range 1-5); median time to progression post-ASCT: 7 months (range 2-29). Four patients had a partial response to treatment (response rate 36%); two patients had stable disease. B symptoms were present at enrollment in four patients and resolved completely on treatment in two patients. Five had disease progression within 3 months of starting treatment. The median duration of response was 9 months (range 0-22 months). Toxicity was mild and limited to grade 2 neuropathy in 6 patients and grade 2 or 3 neutropenia in 4 patients., Conclusions: In this small study in chemotherapy- refractory HL, THAL and VBL demonstrated encouraging activity with some durable responses and acceptable toxicity. These results suggest that chronic low dose chemotherapy combined with less toxic immunomodulatory or anti-angiogenic drugs warrants further study.

Although the prognosis for mantle cell lymphoma (MCL) patients has improved in recent years, the outlook for those with advanced or recurrent disease remains poor. High-dose chemotherapy and autografting performed early in responding patients appears to be a method to extend progression-free survival (PFS) and overall survival (OS). The use of monoclonal antibody therapy added into the initial therapy and in the peritransplant period may improve on these results. Myeloablative allogeneic transplant appears to be a modality capable of providing curative therapy, but is plagued by a high treatment-related mortality, especially in older patients. Reduced-intensity conditioning allografting have fewer problems associated with the initial phase of transplant and hence may be preferred for those patients for whom an allograft is considered but have comorbid conditions or age issues that preclude a full allograft. Long-term results are lacking and the side effects associated with chronic GVHD may be as significant and debilitating. Trials designed to look at newly diagnosed patients with MCL examining the outcomes after planned autologous and allogeneic transplant as part of the initial management are needed to confirm the role of these various modalities in the overall therapy of this poor-outcome lymphoma.

Allogeneic stem cell transplantation has an under-appreciated role in the management of intermediate-grade non-Hodgkin's lymphoma. It provides several advantages over autologous stem cell transplantation including provision of a lymphoma-free graft, reduced rates of secondary myelodysplastic syndrome and leukemia, and a potentially curative graft-versus-lymphoma effect. When applied to chemosensitive patients, the lower relapse rates and reasonable long-term outcomes make allogeneic transplantation a promising therapy to pursue. Patient populations, such as those with bone marrow involvement or very high-risk disease, can be identified as having suboptimal outcomes after autotransplantation and may benefit from such an approach. While the exact role of allogeneic stem cell transplantation remains to be determined, broad recommendations can be suggested for the management of patients with intermediate-grade lymphoma. New approaches to allogeneic transplantation, including the use of matched-unrelated donors and reduced-intensity conditioning regimens, may expand the applicability of this potentially curative modality.

The survival of patients with multiple myeloma ( MM) has improved substantially since the introduction in the late 1980s of high-dose chemotherapy ( HDT) supported by autologous stem cell transplantation ( ASCT). Further improvements have been observed following the availability of immunomodulatory drugs ( IMiD) such as thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib. Here, we summarise the recommendations of the Medical Scientific Advisory Group to the Myeloma Foundation of Australia for patients considered suitable for HDT + ASCT as part of initial therapy. These recommendations incorporate the various phases of treatment: induction, HDT conditioning and maintenance therapy. [ABSTRACT FROM AUTHOR]

Summary: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 ?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.Bone Marrow Transplantation (2004) 33, 271-277. doi:10.1038/sj.bmt.1704344 Published online 1 December 2003 [ABSTRACT FROM AUTHOR]

Presents a study that examined the effectiveness of the cyclophosphamide, etoposide and granulocyte-colony stimulating factor (C+E) to mobilize peripheral blood stem cells (PBSC) for autologous stem cell transplantation in patients with lymphoma. Comparison on netrophil recovery between patients who received high-dose therapy and stem cell transplantation; Reasons behind optimizing PBSC; List of stem cell agents.

We report our experience with the combination of anti-thymocyte globulin (ATGAM) and tacrolimus in the treatment of 20 patients with steroid refractory and dependent acute graft-versus-host disease (GVHD) transplanted between August 1996 and February 2000. All patients received cyclosporine-based GVHD prophylaxis. Thirteen patients developed a maximum of grade IV, five grade III and two grade II acute GVHD, with 15 patients being refractory to steroids and five dependent on steroids. Patients were treated with ATGAM (15 mg/kg for 5 d) and tacrolimus (0·025–0·1 mg/kg/d) in addition to continuation of their high-dose steroids and cessation of their cyclosporine. Within 28 d of treatment, we observed eight complete responses (CR), six partial responses (PR) and six with no response. Overall response (CR + PR) was predicted by GVHD severity. Infectious complications occurred in 80% of patients. The median survival was 86·5 d (range, 21–1081 d) with 35% of patients remaining alive. Survival following combination therapy was significantly more likely in men (P < 0·001), skin-only GVHD (P = 0·027), less severe GVHD (P = 0·048), and in responders to tacrolimus and ATGAM (P < 0·001). In conclusion, concurrent introduction of ATGAM and tacrolimus is a promising therapeutic combination for GVHD refractory to steroids and cyclosporine. [ABSTRACT FROM AUTHOR]

The article discusses the case of a female patient diagnosed with palifermin-induced acanthosis nigricans. The patient was treated for multiple myeloma with melphalan followed by autologous stem cell transplantation. She received palifermin before chemotherapy and after stem cell reinfusion. The patient developed bilateral hyperpigmented hyperkeratotic axillary rash consistent with acanthosis nigricans. The rash resolved over three days following completion of palifermin therapy.