Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study).

Complete response (CR) after treatment for multiple myeloma is associated with superior progression-free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto-HCT) between 2010 and 2012. If patients did not achieve CR after auto-HCT, BD consolidation therapy was added to target CR. After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%). After auto-HCT (n = 34), greater than or equal to CR was achieved in 9 patients (20%) and very good partial response (VGPR) was achieved in 11 (24%). Of the 24 patients who received auto-HCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses. Finally, the maximum response with or without BD consolidation was greater than or equal to CR in 19 (41%), VGPR in 7 (15%), and PR in 6 (13%). Through BD consolidation, CR was achieved in 8 of 11 patients with post-HCT VGPR and in 2 of 12 patients with post-HCT PR. In total, 4 year PFS and overall survival were 43 and 80%, respectively. After adjusting for clinical factors, there was no difference in PFS between CR patients after auto-HCT and BD consolidation, while patients with less than or equal to VGPR after consolidation had a significantly lower PFS. Patients with post-HCT CR showed good PFS, and targeting CR through BD consolidation could improve the CR rate. It would be worthwhile to prospectively compare the efficacy of consolidation only for patients who failed to achieve CR to a universal consolidation strategy.

[Serum ALP elevation early after treatment is a predictor for response in myeloma patients treated with bortezomib].

Several studies have shown the predictive value of elevated serum alkaline phosphatase (ALP) level in multiple myeloma (MM) patients treated with bortezomib (BTZ). We assessed the relationship between changes in ALP levels during treatment and response. Thirty patients treated with BTZ in our hospital were analyzed retrospectively. Of the patients analyzed, 12 were male, median age was 62 years (42-86), and 11 had a history of prior chemotherapy. Eighteen patients were treated with BTZ alone or in combination with dexamethasone, while the others were treated with a combination regimen employing an alkylating agent. Seven patients had undergone autologous stem cell transplantation following BTZ therapy. Ten of 28 patients showed ALP elevation of 25% or more from the baseline at 3 weeks, and 14 of the 28 had this finding at 6 weeks. Four of 5 patients who had achieved VGPR or more showed ALP elevation of 25% or more at 3 weeks, and all five had this finding by 6 weeks. No patient without ALP elevation achieved VGPR or a better response. ALP elevation exceeding 25% from the baseline by day 42 is significantly associated with a treatment response better than VGPR (p=0.019). In conclusion, ALP elevation during BTZ treatment is a valuable prognostic marker.

Repeated donor lymphocyte infusions overcome a myeloid sarcoma of the stomach resulting from a relapse of acute myeloid leukemia after allogeneic cell transplantation in long-term survival of more than 10 years.

A patient with acute myeloid leukemia had a relapse with a myeloid sarcoma of the stomach 32 months after allogeneic bone marrow transplantation. The patient was treated with the first donor lymphocyte infusion (DLI) and one course of induction chemotherapy. Due to severe infectious complication after chemotherapy, the patient could not continue chemotherapy. Subsequently, the patient was treated with a total of 13 cycles of DLI at 1-2 month intervals. Complete remission was achieved and neither relapse nor graft versus host disease has occurred during a follow-up of more than 10 years.

[Cost benefit analysis for prophylactic use of itraconazole versus fluconazole after hematopoietic stem cell transplantation].

Systemic fungal infection (SFI) is now one of the main causes of death from infective complications after hematopoietic stem cell transplantation (HSCT) and the role of prophylaxis of fungal infection has been established. However, there is no evidence evaluating the cost-benefit ratio of SFI management in Japan. To estimate the medical costs on prophylaxis and treatment of SFI in HSCT, we embarked on a randomized control prospective study of the medical cost-benefit ratio comparing fluconazole with itraconazole for antifungal prophylaxis in 40 patients who received HSCT in our hospital. Despite the similarity of efficacy for prophylaxis, the median cost of itraconazole prophylaxis between Day-10 and Day+28 was significantly less than that of fluconazole. There are many patients who require an i.v. formulation because of non-compliance with oral administration after HSCT and these cases cause increased medical costs. Therefore, further investigation is needed not only regarding differences among prophylactic agents but also regarding differences in administration routes focusing on the cost-effectiveness of treatment.

Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia.

A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.