Modified CVAD and modified CBAD compared to high-dose cyclophosphamide for peripheral blood stem cell mobilization in patients with multiple myeloma.

BACKGROUND: The optimal regimen for peripheral blood stem cell (PBSC) mobilization in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) has not been established. Experience at The University of Texas MD Anderson Cancer Center suggests in addition to single-agent cyclophosphamide (Cy), modified cyclophosphamide, vincristine, doxorubicin, and dexamethasone (mCVAD), and modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone (mCBAD) may be successful chemomobilization regimens. METHODS: This retrospective review included 167 patients (66 with Cy, 74 with mCVAD, and 27 with mCBAD) with multiple myeloma undergoing mobilization for auto-HCT between January 1, 2006 and September 30, 2013. The primary objective was to evaluate and compare the successful mobilization of CD34+ cells among high-dose Cy, mCVAD or mCBAD. RESULTS: Successful mobilization (≥2×106 CD34+ cells/kg) was achieved in all patients, while 65 (98%), 72 (97%), and 27 (100%) patients achieved an optimal mobilization (≥4×106 CD34+ cells/kg) in the Cy, mCVAD, and mCBAD groups, respectively. There was no significant difference in the number of apheresis sessions (P=.63), incidence of febrile neutropenia (P=.57), or hospital admission rates (P=.55). CONCLUSION: Either Cy, mCVAD, or mCBAD can yield successful PBSC mobilization in patients with multiple myeloma undergoing auto-HCT.

A case series using famciclovir in stem cell transplant recipients with valacyclovir hypersensitivity reactions.

BACKGROUND: Herpes simplex virus and varicella zoster virus reactivation can occur in up to 32% and 40% of patients, respectively in the first year post-transplant without prophylaxis. Antiviral therapy consisting of acyclovir or valacyclovir is recommended for at least 1 year post stem cell transplant per evidence-based guidelines. OBJECTIVE: In the event of a contraindication or hypersensitivity reaction to either drug, an alternative is essential based on the proven efficacy in reducing clinically significant herpes simplex virus and varicella zoster virus reactivations. We report two cases of successful initiation of famciclovir in stem cell transplant recipients experiencing hypersensitivity to valacyclovir or acyclovir. DISCUSSION: In both cases, there were no hypersensitivity reactions or breakthrough viral infections after famciclovir initiation but this observation is limited by a small patient population. CONCLUSION: Due to the limited data available, famciclovir appears to be a reasonable option in immunocompromised patients with a mild valacyclovir or acyclovir hypersensitivity reaction.

The impact of pre-transplant valganciclovir on early cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus reactivation is a common complication of allogeneic hematopoietic stem cell transplant. The use of pre-transplant valganciclovir during the conditioning regimen followed by preemptive therapy has been used in an attempt to reduce the rate of early cytomegalovirus reactivation, but efficacy data are lacking. In this retrospective study, we evaluated the impact of pre-transplant valganciclovir during the conditioning regimen followed by a preemptive approach on the rate of early cytomegalovirus reactivation through day 100. The rate of cytomegalovirus reactivation through day 100 was 41% in the no-valganciclovir group compared to 46% in the valganciclovir group (p = 0.4). Interestingly, median time to cytomegalovirus reactivation was earlier in the no-valganciclovir group compared to the valganciclovir group (26 vs. 34 days; p = 0.008) and there was a trend toward a higher rate of cytomegalovirus disease through day 100 in the no-valganciclovir group (0.7% valganciclovir vs. 4% no-valganciclovir; p = 0.1). Day 100 survival was similar between the groups (90% valganciclovir vs. 91% no-valganciclovir; p = 0.8). Although the time to cytomegalovirus reactivation is significantly longer in the valganciclovir group, this did not impact the rate of cytomegalovirus reactivation or survival by day 100 suggesting that other strategies need to be explored.

Feasibility of allografting in patients with advanced acute lymphoblastic leukemia after salvage therapy with inotuzumab ozogamicin.

BACKGROUND: No highly effective salvage therapy exists for patients with relapsed acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody attached to calicheamycin that targets B lymphocytes in early stages of development, successfully inducing remission in patients with multiply relapsed ALL. METHODS: We describe our findings in 26 patients who received allogeneic hematopoietic stem cell transplantation (SCT) after treatment with IO between September 2010 and October 2011. RESULTS: Patients with a median age of 33 years (range, 5-70 years) received an allogeneic matched sibling donor (n = 9), matched- or 1-antigen mismatched unrelated donor (n = 16), or cord blood donor SCT (n = 1) while in complete remission (n = 23) or with active disease (n = 3). At the time of SCT, 15 patients were in complete remission without evidence of minimal residual disease (MRD) measured by multiparameter flow cytometry. Patients were heavily pretreated, including 5 patients who had received previous allogeneic SCT. Patients received a median of 3 courses of IO (range, 1-5 courses) before SCT. Seven patients are alive at a median follow-up of 13 months (range, 5-16 months), with 1-year event-free and overall survival (OS) of 22% and 20%, respectively. Patients without MRD at time of SCT had a markedly better 1-year OS of 42%. The cumulative incidence of nonrelapse mortality (NRM) at 6 months and 1 year were 40% and 60%, respectively, with 5 deaths attributed to venoocclusive disease (VOD). CONCLUSIONS: Treatment with IO allows more patients to undergo transplantation while in remission, with favorable overall survival in patients without MRD who undergo transplantation. Reduction in hepatic toxicity is needed to improve overall results.

A review of pharmacologic options for previously untreated chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and has a heterogeneous clinical course. Some patients experience an indolent disease course, which does not require treatment or affect their overall quality of life. Other patients present with symptomatic advanced disease that rapidly progresses and requires therapy. For these patients, chemotherapy is the mainstay of treatment and has undergone significant evolution in the past few decades. From alkylating agents to purine analogs, response rates have greatly improved with new chemotherapy regimens. The development of chemoimmunotherapy regimens has also transformed the treatment of CLL. This article will review front-line treatment options for CLL and discuss the updated National Comprehensive Cancer Network guidelines.