Muthu Veeraputhiran

Rhabdomyolysis Resulting from Pharmacologic Interaction Between Erlotinib and Simvastatin

Erlotinib is an epidermal growth factor receptor inhibitor indicated as a second line of therapy for locally advanced and metastatic non-small-cell lung cancer after the failure of 1 previous chemotherpy. Simvastatin belongs to the statin family used to lower blood cholesterol. Drug interaction between erlotinib and statin has not been reported before. Both drugs are major substrates of the CYP3A4 enzyme in the liver. Thus, co-administration of these drugs can increase their serum levels, potentially leading to adverse effects. We report the interaction between erlotinib and simvastatin leading to rhabdomyolysis. Thus, caution is required with increasing usage of both of these drugs.

Viability and engraftment of hematopoietic progenitor cells after long-term cryopreservation: effect of diagnosis and percentage dimethyl sulfoxide concentration

BACKGROUND AIMS We carried out a retrospective analysis of viability by diagnosis and dimethyl sulfoxide (DMSO) concentration in patients who had undergone autologous transplants using hematopoietic progenitor cells (HPC) after long-term storage (up to 17.8 years). METHODS Viability was tested using flow cytometry for HPC that were harvested and preserved using a controlled rate freezer and 5% or 10% DMSO with human serum albumin, then stored in liquid nitrogen. Data from 262 samples were analyzed (249 myeloma patients and 13 other diagnoses): 100 consecutively thawed samples with a storage time of <1 year (all 10% DMSO), 50 consecutive samples stored for 1-4.9 years (10% DMSO), 50 samples stored for 5-9 years (5% DMSO) and all samples stored and used for transplant after >9 years (60 samples, 5% DMSO; two samples, 10% DMSO). RESULTS No statistically significant difference in viability between the 5% DMSO and 10% DMSO groups was observed (P = 0.08), so the 1-4.9 years and 5-9 years were combined and the three groups (<1 year, 1-9 years and >9 years) were compared using an anova test. There was no difference in viability based on cryostorage period (P = 0.23) or between myeloma and other diagnoses (P = 0.45). No difference was seen in time to White blood cell (WBC) engraftment (P = 0.10) or to platelet engraftment between groups (P = 0.52). CONCLUSIONS These data suggest that long-term storage in 5% DMSO and human serum albumin is safe.

A comparison of washed and volume-reduced platelets with respect to platelet activation, aggregation, and plasma protein removal.

BACKGROUND: Washed or volume‐reduced platelets (PLTs) are occasionally requested for patients with a history of allergic or anaphylactic transfusion reactions. However, conclusive data are not available as to which method is more suitable.

Bronchoscopy can be done safely in patients with thrombocytopenia

Prophylactic platelet (PLT) transfusions are often administered to patients before bronchoscopy or bronchoalveolar lavage (BAL) to prevent bleeding. There is a paucity of data to validate this approach, with a commonly suggested PLT transfusion threshold of fewer than 50 × 109/L, largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in patients with thrombocytopenia undergoing bronchoscopy.

BEAM Conditioning Regimen Has Higher Toxicity Compared With High-Dose Melphalan for Salvage Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

BACKGROUND Salvage autologous stem cell transplantation (ASCT) is increasingly used for eligible patients with multiple myeloma (MM) for progress after conventional chemotherapy. We recently used BEAM (BCNU, etoposide, cytarabine, and melphalan) conditioning for patients with myeloma receiving salvage ASCT whose disease progressed after a first ASCT with high-dose melphalan (HDM). We report safety and efficacy of BEAM salvage ASCT in MM in comparison with HDM-based salvage ASCT. PATIENTS AND METHODS Between 2008 and 2013, 43 consecutive patients received salvage ASCT for MM (19 with HDM; 24 with BEAM). RESULTS The BEAM group had a higher incidence of infections, intensive level of care, and fever (19 vs. 13 patients; P = .02), whereas the melphalan group had a higher incidence of mucositis (7 vs. 2 patients; P = .03). Other toxicities were not different. There was no significant difference in disease status and response rate before and after salvage ASCT between the 2 groups. The median time of follow-up after salvage ASCT was 5 and 9 months and the median progression-free survival (PFS) times were 7.7 and 12.1 months (P = .82) for BEAM and melphalan, respectively. CONCLUSION BEAM seemed to be associated with higher toxicity with comparable efficacy to HDM ASCT. Longer follow-up is needed to determine whether there is any significant difference in PFS between the 2 groups.

Aldehyde dehydrogenase as an alternative to enumeration of total and viable CD34+ cells in autologous hematopoietic progenitor cell transplantation

We validated the correlation of aldehyde dehydrogenase ALDH(br) cells with total and viable CD34(+) cells in fresh and thawed hematopoietic progenitor cell (HPC) products, and looked for a correlation with time to white blood cell (WBC) and platelet engraftment after autologous transplantation, using simple linear regression analyzes. We found a significant correlation between pre-freeze ALDH(br) cell numbers and pre-freeze total CD34(+) (P < 0.001), viable CD34(+) (P < 0.001) and post-thaw viable CD34(+) (P < 0.001) cell numbers. We suggest that ALDH(br) may be substituted for CD34(+) cell numbers when evaluating HPC. As post-thaw viability testing apparently adds no significant information, we suggest that it may not be necessary. Finally, neither marker correlated with time to engraftment in our patients, supporting previous data suggesting the existence of a threshold dose for timely engraftment around 2.5 × 10(6) cells/kg.

Validation of the Hematopoietic Cell Transplantation–Specific Comorbidity Index in Nonmyeloablative Allogeneic Stem Cell Transplantation

The Hematopoietic Cell Transplantation (HCT)-Specific Comorbidity Index (HCT-CI) has been extensively studied in myeloablative and reduced-intensity conditioning regimens, with less data available regarding the validity of HCT-CI in nonmyeloablative (NMA) allogeneic transplantation. We conducted a retrospective analysis to evaluate the association between HCT-CI and nonrelapse mortality (NRM) and all-cause mortality (ACM) in patients receiving the total lymphoid irradiation and antithymocyte globulin (TLI/ATG) NMA transplantation preparative regimen. We abstracted demographic and clinical data from consecutive patients, who received allogeneic HCT with the TLI/ATG regimen between January 2008 and September 2014, from the Stanford blood and marrow transplantation database. We conducted univariable and multivariable Cox proportional hazards regression models to evaluate the association between HCT-CI and NRM and ACM. In all, 287 patients were included for analysis. The median age of the patients was 61 (range, 22 to 77) years. The median overall survival was 844 (range, 374 to 1484) days. Most patients had Karnofsky performance score of 90 or above (85%). Fifty-two (18%) patients relapsed within 3 months and 108 (38%) patients relapsed within 1 year, with a median time to relapse of 163 (range, 83 to 366) days. Among the comorbidities in the HCT-CI identified at the time of HCT, reduced pulmonary function was the most common (n = 89), followed by prior history of malignancy (n = 39), psychiatric condition (n = 38), and diabetes (n = 31). Patients with higher HCT-CI scores had higher mortality risks for ACM (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.22 to 3.14 for HCT-CI score 1 or 2 and HR, 1.85; 95% CI, 1.11 to 3.08 for HCT-CI score ≥ 3, compared with 0, respectively). Among individual HCT-CI variables, diabetes (HR, 2.31; 95% CI, 1.79 to 2.89; P = .003) and prior solid tumors (HR, 1.75; 95% CI, 1.02 to 3.00; P = .043) were associated with a higher risk of ACM. Higher HCT-CI scores were significantly associated with higher risk of death. HCT-CI is a valid tool for predicting ACM in NMA TLI/ATG allogeneic HCT.

Successful hematopoietic stem cell collection in patients who fail initial plerixafor mobilization for autologous stem cell transplant.

We report our experience of collecting stem cells in patients who failed to mobilize sufficient hematopoietic stem cell (HSC) using plerixafor (P) in the initial mobilization attempt. Twenty four patients were identified who failed a first mobilization attempt using P. Of these, 22 patients received granulocyte colony stimulating factor (G‐CSF) and two patients received cyclophosphamide (CY) + G‐CSF in combination with P for the initial attempt. The agents used for second collection attempt were granulocyte macrophage colony stimulating factor (GM‐CSF) + G‐CSF (19 patients), G‐CSF + P (three patients), CY + G‐CSF (one patient), and bone marrow harvest (one patient). A median of 0.6 × 106 CD34+ cells/kg (range 0–1.97) were collected in the initial attempt. A second collection was attempted at a median of 22 days (range 15–127) after the first failed mobilization. The median CD34+ cell dose collected with the second attempt was 1.1 × 106 CD34+ cells/kg (range 0–7.2). A third collection was attempted in six patients at median of 51 days (range 34–163) after the first failed mobilization. These patients collected a median of 1.1 × 106 CD34+ cells/kg (range 0–6.5). Total of 16 patients (67%) collected sufficient cells to undergo autologous stem cell transplant and eight patients (33%) were able to collect ≥2 × 106 CD34+ cells/kg in a single subsequent attempt. Our experience suggests that a majority of patients who fail primary mobilization despite use of P can collect sufficient HSC with a subsequent attempt using combination of G‐CSF with either P or GM‐CSF. J. Clin. Apheresis 29:293–298 2014.

Strict vs lenient criteria for elution testing: comparison of yields between two tertiary care medical centers.

In this study, 2 patient populations, using different elution strategies, were compared to evaluate eluate yields under more and less restrictive conditions. An informative eluate was defined as one in which an antibody that could be clinically significant was detected in the eluate but was not detectable in the plasma at the time of elution testing. The results for 160 direct antiglobulin tests (DATs) and 160 elution studies were evaluated in 71 patients at the adult hospital (lenient criteria). The results for 372 DATs and 43 elution studies were evaluated in 123 patients at the pediatric hospital (strict criteria). The yields from these eluates were 0.6% at the adult hospital (C antibody) vs 2.3% at the pediatric hospital (Jk(a) antibody). Thus, the yield of information from eluate testing is low regardless of the stringency applied to testing. However, considering the cost and time required for testing, more stringent criteria are advised.

Cytomegalovirus appendicitis after hematopoietic stem cell transplantation

We present the case of a young man with acute lymphoblastic leukemia who developed cytomegalovirus (CMV) appendicitis after receiving alemtuzumab for acute refractory graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation (HSCT). CMV appendicitis is a rare complication; and we are reporting the first case to our knowledge of CMV appendicitis following HSCT. Our case highlights the importance of recognition of CMV viral reactivation following the use of alemtuzumab. Using a preemptive strategy of checking CMV PCR, with initiation of early effective treatment on detection of CMV replication, may be appropriate following use of alemtuzumab in hematologic malignancies in patients after HSCT.