Cytomegalovirus (CMV) disease causes significant morbidity among solid organ transplant (SOT) recipients. To prevent CMV disease, eligible recipients are frequently started on valganciclovir (VGC) prophylaxis post-transplant. Leukopenia has been documented as a primary adverse events of the drug (1). This study's primary aim was to determine whether a patient's weight at the start of VGC prophylaxis was associated with the development of leukopenia.

This was a single center, retrospective cohort study that included adults > 18 years of age, who had received an organ transplant (heart, liver, or lung) at an academic transplant center from January 1, 2018 through December 31, 2022. A creatinine clearance of > 60 mL/min was required.

All 294 included patients received 900 mg/day of VGC for CMV prophylaxis, without dose adjustment. Fifty-two percent of the patients developed leukopenia while receiving VGC prophylaxis. The mean weight at initiation of VGC was higher in patients who did not develop leukopenia (97.9 kg) compared to those who did (90.7 kg; p = 0.0112). It was found that with each 1 kg increase in body weight, the likelihood of developing leukopenia decreased by 1.7% (p = 0.004, odds ratio = 0.983, 95% confidence interval [CI], 0.972-0.994). Patients with a baseline body-mass index (BMI) > 25 had a longer median freedom time from leukopenia after initiation of VGC as compared to the group with baseline BMI < 25 (log-rank p = 0.035).

These data suggest that in SOT recipients with normal renal function, receiving a fixed dose of VGC resulted in a significant, inverse relationship between body weight and the development of leukopenia.

Neutropenia is a frequent complication among solid organ transplant (SOT) recipients receiving immunosuppressive therapy and antimicrobial prophylaxis. However, there are limited studies analysing the frequency and impact of neutropenia in lung transplant recipients (LTRs). Our aim was to analyse the frequency of neutropenia, the need for granulocyte colony-stimulating factor (GCSF) treatment within the first 18 months post-transplant and its association with acute rejection, chronic lung allograft dysfunction (CLAD), overall survival and the development of infections.

This observational and retrospective study recruited 305 patients who underwent lung transplantation between 2009 and 2019, with outpatient quarterly follow-up during the first 18 months post-surgery.

During this period, 51.8% of patients experienced at least one episode of neutropenia. Neutropenia was classified as mild in 50.57% of cases, moderate in 36.88% and severe in 12.54%. GCSF treatment was indicated in 23.28% of patients, with a mean dose of 3.53 units. No statistically significant association was observed between neutropenia or its severity and the development of acute rejection, CLAD or overall survival. However, the patients who received GCSF treatment had a higher mortality rate compared to those who did not. Sixteen patients (5.25%) developed infections during neutropenia, with bacterial infections being the most common.

Neutropenia is common in the first 18 months after lung transplantation and most episodes are mild. We did not find an association between neutropenia and acute rejection, CLAD, or mortality. However, the use of GCSF were associated with worse post-transplant survival.

This review summarizes the factors influencing the efficacy and safety of the COVID-19 vaccine in LTR through meta-analysis, hoping to provide strategies for vaccine use.

Electronic databases were screened for studies on mRNA vaccines in LTR. The primary outcome was the pooled seroconversion rate, and the secondary outcome was the incidence of adverse events+breakthrough infections. Subgroup analyses were made based on BMI, associated comorbidities, presence of baseline leukopenia, time since transplant, and drugs used.

In total, 31 articles got included. The pooled seroconversion rate after at least two doses of SARS-CoV-2 vaccination was 72% (95% CI [0.52-0.91). With significant heterogeneity among studies I2 = 99.9%, the seroconversion rate was about 72% (95%CI [0.66-0.75]), from the studies reporting two doses of vaccine slightly higher around 75%(95%CI [0.29-1.22]) from studies reporting three doses. The pooled seroconversion rate within the lower to normal BMI group was 74% (95% CI [0.22-1.27], Pi=0.005) against 67% (95% CI [0.52-0.81], Pi=0.000) in the high BMI group. The pooled seroconversion rate in the ''positive leukopenia'' group was the lowest, 59%. Leukopenia could influence the vaccine seroconversion rate in LTR. From the time since transplant analysis after setting seven years as cut off point, the pooled seroconversion rate after at least two doses of COVID-19 vaccination was 53% (95% CI [0.18-0.83], P=0.003, I2 = 99.6%) in <7years group and 83% (95% CI [0.76-0.90], P=0.000 I2 = 95.7%) in > 7years group. The only time since transplantation had reached statistical significance to be considered a risk factor predictor of poor serological response (OR=1.27 95%CI [1.03-1.55], P=0.024). The breakthrough infection rate after vaccination was very low2% (95% CI 0.01-0.03, I2 = 63.0%), and the overall incidence of adverse events, which included mainly pain at the injection site and fatigue, was 18% (95%CI [0.11-0.25], I2 = 98.6%, Pi=0.000).

The seroconversion rate in LTR vaccinated with at least two doses of mRNA COVID-19 vaccine could be significantly affected by the vaccine type, immunosuppressant used, BMI, leukopenia, associated comorbidities, and time since transplantation. Nevertheless, booster doses are still recommended for LTR.

Neutropenia is generally defined as an absolute neutrophil count in the circulation of less than 1500/mm³ and occurs in up to 25%-30% of pediatric solid organ transplant recipients (SOT) within the first year after transplantation. In the SOT population, neutropenia is most often a result of drug-induced bone marrow suppression but can also be secondary to viral infection, nutritional deficiencies, lymphoproliferative infiltrate, and inherited causes. Outcomes for patients with neutropenia vary by degree of neutropenia and type of solid organ transplant. Management of neutropenia should begin by addressing the underlying cause, including reducing or removing medications when appropriate, treating infections, and addressing nutrient deficiencies; however, consultation with an experienced pediatric hematologist and use of granulocyte colony-stimulating factor (G-CSF) may be helpful in some cases. Overall, data on clinical outcomes for G-CSF use remain limited, but observational studies may support its use in patients with infections or severe neutropenia.

While prior adult studies have shown that approximately 20%-38% of subjects undergoing solid-organ transplant develop neutropenia, similar analyses in pediatric subjects are scarce.

We conducted a retrospective chart review of liver transplant (LT) and kidney transplant (KT) recipients at our center during the period 2008-2018. All of the KT and none of the LT subjects during this time period had induction with either anti-thymocyte globulin (ATG) or basiliximab at time of transplant. Neutropenia was defined as absolute neutrophil count (ANC) value ≤1000/mm3 .

One hundred subjects with LT and 82 subjects with KT were included. The incidence of neutropenia within the first year of transplant in KT was higher compared to LT (54.8% vs 39%, p = .01). The median number of hospitalizations (p = .001) and infectious complications (p = .04) was significantly higher only in the KT subjects who developed neutropenia (compared to those who did not). Multivariate analysis identified factors associated with severity of liver disease at transplant, namely h/o upper gastrointestinal bleeding (p = .02), weight deficit (p = .01), and pre-LT ANC (p = .01), along with high or moderate risk cytomegalovirus status (p = .05) as predictors of neutropenia in LT subjects. Female gender (p = .03) predicted neutropenia, while BK virus infection was protective for neutropenia (p = .04) in KT subjects.

The incidence of and morbidity associated with neutropenia within 1 year post-transplant is higher in KT subjects compared to LT subjects. The likely reason for this is the use of induction therapy (ATG, basiliximab) at the time of transplant in KT subjects.

Neutropenia is a serious complication following heart transplantation (OHT); however, risk factors for its development and its association with outcomes is not well described. We sought to study the prevalence of neutropenia, risk factors associated with its development, and its impact on infection, rejection, and survival.

A retrospective single-center analysis of adult OHT recipients from July 2004 to December 2017 was performed. Demographic, laboratory, medication, infection, rejection, and survival data were collected for 1 year post-OHT. Baseline laboratory measurements were collected within the 24 hours before OHT. Neutropenia was defined as absolute neutrophil count ≤1000 cells/mm3. Cox proportional hazards models explored associations with time to first neutropenia. Associations between neutropenia, analyzed as a time-dependent covariate, with secondary outcomes of time to infection, rejection, or death were also examined.

Of 278 OHT recipients, 84 (30%) developed neutropenia at a median of 142 days (range 81-228) after transplant. Factors independently associated with increased risk of neutropenia included lower baseline WBC (HR 1.12; 95% CI 1.11-1.24), pre-OHT ventricular assist device (1.63; 1.00-2.66), high-risk CMV serostatus [donor positive, recipient negative] (1.86; 1.19-2.88), and having a previous CMV infection (4.07; 3.92-13.7).

Neutropenia is a fairly common occurrence after adult OHT. CMV infection was associated with subsequent neutropenia, however, no statistically significant differences in outcomes were found between neutropenic and non-neutropenic patients in this small study. It remains to be determined in future studies if medication changes in response to neutropenia would impact patient outcomes.

The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation (LT). However, splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly.

To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism.

Between October 2015 and February 2019, 762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital. Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism. Among these patients, 41 received partial splenectomy during LT (PSLT group), and 43 received only LT (LT group). Patient characteristics, intraoperative parameters, and postoperative outcomes were retrospectively analyzed and compared between the two groups.

The incidence of postoperative hypersplenism (2/41, 4.8%) and recurrent ascites (1/41, 2.4%) in the PSLT group was significantly lower than that in the LT group (22/43, 51.2%; 8/43, 18.6%, respectively). Seventeen patients (17/43, 39.5%) in the LT group required two-stage splenic embolization, and further splenectomy was required in 6 of them. The operation time and intraoperative blood loss in the PSLT group (8.6 ± 1.3 h; 640.8 ± 347.3 mL) were relatively increased compared with the LT group (6.8 ± 0.9 h; 349.4 ± 116.1 mL). The incidence of postoperative bleeding, pulmonary infection, thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group, respectively.

Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.

No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single-center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm³ in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post-transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High-risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18-3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52-1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16-2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97-2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.

Neutropenia after orthotopic liver transplantation (LT) is relatively common, but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] ≤ 1000/mm(3) ) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, bloodstream infection (BSI), invasive fungal infection, cytomegalovirus (CMV) disease, and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC < 500/mm(3) ). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (hazard ratio [HR] 1.15; 95% confidence interval [CI], 1.03-1.30; P = 0.02), BSI (HR, 2.89; 95% CI, 1.63-5.11; P < 0.001), CMV disease (HR, 4.28; 95% CI, 1.55-11.81; P = 0.005), baseline tacrolimus trough level (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and later era LT (2004-2009 versus 1999-2003; HR, 2.28; 95% CI, 1.43-3.65; P < 0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR, 3.76; 95% CI, 1.84-7.68; P < 0.001). In conclusion, our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality.

To evaluate the incidence of bone marrow suppression and consequences of MMF dose adjustment in patients within the first year after heart transplantation.

Group I (n=47) was treated with a regimen currently used in patients after heart transplantation (mycophenolatemofetil - MMF, valganciclovir - VGC and trimethoprim/sulfamethoxazole - TMP-SMX). Group II (n=47) received only MMF of potentially myelotoxic medications. The myelotoxic effect and need for dose modification were assessed. The incidence of rejections and infectious episodes associated with MMF adjustment were analyzed during the first 12 months in Group I.

There was a significantly greater proportion of patients with leukopenia (leukocyte count < 4 x 10^9/L) at 3 months after orthotopic heart transplantation in Group I compared with Group II (19.1% vs 2.1%; P = 0.02). The difference in lymphopenia (lymphocyte count < 0.8 x 10^9/L) at 3 months follow-up was highly significant (38.3 % vs 6.4 %; P = 0.0002). MMF was modified due to bone marrow suppression or severe infection in 63.8% patients in Group I and in only 8.5% of patients in Group II (P < 0.001). Reducing or stopping MMF was not associated with increased rejections. In Group I, at least 1 episode of higher degree cellular or humoral rejection occurred in 35% of patients with the standard MMF dosage compared with only 26% in patients with modified MMF (P = 0.0534).

Addition of VGC+TMP-SMX to current immunosuppressive medication regimen in patients after heart transplantation is associated with significant lymphocytopenia and leukopenia. Importantly, modification of immunosuppressive prophylaxis (reducing or stopping MMF) leads to normalization of blood count without increased incidence of rejections.

To assess the differences in rejection and infection complications between the most common contemporary immunosuppression regimen in pediatric heart transplantation (cytolytic induction, tacrolimus based) and classic triple-therapy (cyclosporine based without induction).

We performed a retrospective, historical-control, observational study comparing outcomes in patients who underwent traditional immunosuppression (control group, n = 64) with those for whom the contemporary protocol was used (n = 39). Episodes of rejection, viremia (cytomegalovirus or Epstein-Barr virus), serious bacterial or fungal infections, anemia or neutropenia requiring treatment in the first year after heart transplantation, and 1-year survival were compared between traditional and contemporary immunosuppression groups.

The 2 groups were similar with respect to baseline demographics. There were no differences in risk of cytomegalovirus, Epstein-Barr virus, or bacterial or fungal infections in the first year post-transplantation. Patients in the contemporary group were more likely to need therapy for anemia (51% vs 14%, P < .001) or neutropenia (10% vs 0%, P = .019). However, more contemporary protocol patients were rejection-free in the first year post-transplantation (63% vs 41%, P = .03). Overall graft survival was similar between groups (P = .15).

A contemporary immunosuppression regimen using tacrolimus, mycophenolate mofetil, and induction was associated with less rejection in the first year, with no difference in the risk of infection but greater risk of anemia and neutropenia requiring treatment. Long-term follow-up on these patients will evaluate the impact of the immunosuppression regimen on survival.

Assessing the value of mycophenolic acid (MPA) monitoring outside renal transplantation is hindered by the absence of any trial comparing fixed-dose and concentration-controlled therapy. However, in liver and thoracic transplantation particularly, clinical trials, observational studies with comparison groups, and case series have described MPA efficacy, exposure/efficacy relationships, pharmacokinetic variability, and clinical outcomes relating to plasma MPA concentrations. On the basis of this evidence, this report identifies MPA as an immunosuppressant for which the combination of variable disposition, efficacy, and adverse effects contributes to interindividual differences seemingly in excess of those optimal for a fixed-dosage mycophenolate regimen. Combined with experiences of MPA monitoring in other transplant indications, the data have been rationalized to define circumstances in which measurement of MPA concentrations can contribute to improved management of mycophenolate therapy in nonrenal transplant recipients.