On February 9, she received induction chemotherapy with VIP regimen (vincristine, idarubicin, and dexamethasone) and successfully achieved CR.Next, consolidation chemotherapy including VILP (VIP+ asparaginase) and hyper-CVAD regimen was performed. The patient refused allo-HSCT at the time of the first CR.In November 2016, bone marrow examination showed 41% lymphoblastic cells, indicating leukemia relapse.After re-induction therapy with VILP regimen, the patient attained her second CR. She subsequently underwent an umbilical cord blood transplantation (UCBT) in May 2017. Allografts were from a 4/6 HLA-matched unrelated umbilical cord blood according to low-resolution. The doses of total nucleated cells and CD34+ cells infused were 3.9×107/kg and 3.0×105/kg, respectively. The conditioning regimen included intravenous busulfan at 3.2 mg/kg/d for 4 days, cyclophosphamide at 60 mg/kg daily for 2 days, and fludarabine at 30 mg/m2 daily for 4 days. Cyclosporine and mycophenolate mofetil were used for GVHD prophylaxis. Neutrophil and platelet engraftment was observed on day 22 and day 37 after umbilical cord blood infusion, respectively. The patient maintained CR for 19 months with complete donor chimerism and without graft-versus-host disease.However, in January 2019, 21% of lymphoblasts were detected in the bone marrow by morphological analysis and flow cytometry. The patient relapsed again after UCBT. Intriguingly, chimerism testing using short tandem repeats still showed complete donor chimerism at this time point. This was termed “donor cell-derived leukemia”(DCL). Chemotherapy with VIP regimen failed to induce remission (32% lymphoblasts in bone marrow). The patient had no opportunity for second transplantation due to lack of available donors. CAR-T cell therapy was recommended for the patient. She was enrolled in our clinical trial of anti-CD19 CAR-T cell therapy. The patient received lymphodepletion pretreatment with FC regimen (fludarabine 30 mg/m2 daily for 3 days, cyclophosphamide 300 mg/m2 daily for 3 days) from March 13, 2019 to March 15, 2019. After the lymphodepletion pretreatment, anti-CD19 CAR-T cells were infused at a total dose of 2.0×106/kg for 3 consecutive days (0.2×106/kg at day 0, 0.6×106/kg at day 1, 1.2×106/kg at day 2). Body temperature, cytokine levels, and c-reactive protein (CRP) were monitored. The patient developed a fever with a maximum body temperature of 38°C on day 6. The temperature rose to 39°C and the blood pressure dropped to 83/58 mmHg on day 7. The patient was diagnosed with grade 2 cytokine release syndrome (CRS). Non-steroidal anti-inflammatory drugs (NSAIDs) and tocilizumab (8 mg/kg) were used for CRS. Afterward, the temperature dropped gradually and returned to normal after a week. The highest serum level of interleukin 6 (IL-6) was 363 pg/mL on day 7. The copy number of anti-CD19 CAR in peripheral blood reached its peak on day 10, which was 1.08×105 copies/μg.DNA. On April 4, 2019 (day 17), the bone marrow smear found no lymphoblast, and FCM revealed MRD negative (MRD<0.01% by 8-color flow cytometry). On day 118 after CAR-T cells infusion, the copy number of CAR was not detected. The patient remained in MRD-negative status for 5 months. On August 20, 2019, flow cytometry examination showed MRD levels of 0.05% for 2 consecutive bone marrow samples within a 1-month interval. The immunophenotype of MRD was CD34+CD10+CD19+CD22+ CD58dim CD20-CD123-. Given the increased MRD levels, the patient was given 3 million IU of interferon-α-2b, three times a week. She achieved MRD negative again after 42 days of interferon-alpha treatment. Interferon-α-2b was used for 2 years. Notably, analysis of immune cell subsets from peripheral blood showed a significant increase in the proportion of CD16+ CD56+ NK cells. To date, the patient has maintained CR for 41 months after CAR-T cells followed by interferon-α therapy. No adverse reactions were observed during interferon-α treatment. The patient is still under follow-up now.

The present case suggested that anti-CD19 CAR-T cell followed by interferon-α treatment was effective in donor cell-derived B-ALL, Can sequential interferon-α therapy helps maintain durable remission in all leukemia patients who relapse after allo-HSCT?

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Hello everyone

I have a question regarding the Covid vaccine (Pfizer-BioNTech) and its side effects. Has anyone had this experience and know what to do in this situation. 

Below is a summary.

Patient is 27 years old, generally healthy, 10 days before first vaccination against COVID - Pfizer-Biontech vaccine, which took place on 09.07.2021, he finished several weeks of treatment with heparin due to a fracture of the shin bone (he has an implant). During the first 3 days nothing alarming happened. On the 4th day after vaccination he started to have a fever of 39-39.5 C, severe headache, muscle pain, nausea and weakness. This condition lasted 3 days (headache responded well to NSAIDs). On the 7th day after vaccination, the tests revealed a decrease in leukocytes to 3,000 and platelets to 109,000, elevated transaminases to about 150 iu/l and CRP 3 times above normal. After another three days platelets, leukocytes and CRP normalized. At 2 weeks after vaccination, transaminases increased to 300 iu/l (with normalization during the next 2 weeks) and D-dimers were 8971 (normal to 500). D-dimers gradually decreased (to 820 on 06.08.21). During further observation the result was normal. At that time two antigen tests were negative. 

Antibodies to SARC-COV-2 against S protein in IgG class after 4 week after vaccination were 578 (n< 33.8), after 10 week. 290.

On the order of a hematologist ( 5 months after vaccination ):

1.Anti-SARS-CoV-2 IgM and IgG NCP ELISA antibodies - negative result.

2. antibodies to PF4 negative.

3.Ultrasound - no venous thrombosis in lower limbs.  

According to the hematologist, there are no absolute contraindications to vaccination, but he recommends "caution". However, he is unable to advise us on a safe course of action or the cause of the abnormalities (it is now too late to unequivocally confirm or exclude HITT and VITT)

Thanks for your help in advance

Tomasz Rywik

FRIDAY, March 3, 2023 (HealthDay News) -- For adults with acute lower back pain (LBP), myorelaxants, nonsteroidal anti-inflammatory drugs (NSAIDS), and NSAIDs combined with acetaminophen can reduce pain and disability, according to a review published online Feb. 22 in the Journal of Orthopaedic Research.

Alice Baroncini, M.D., Ph.D., from RWTH University Hospital in Aachen, Germany, and colleagues conducted a systematic review to examine whether pharmacological management of acute LBP can effectively reduce pain and disability and which drugs have the highest efficacy. All randomized controlled trials examining the efficacy of myorelaxants, NSAIDs, and acetaminophen for acute (less than 12 weeks) LBP of the lumbar spine in adults were included; studies assessing opioid use in acute LBP were not included. Data were obtained from 18 trials with 3,478 patients.

The researchers found that at approximately one week, myorelaxants and NSAIDs were effective for reducing pain and disability in acute LBP. Greater improvement was seen with the combination of NSAIDs and acetaminophen than with NSAIDs alone, while no significant improvement was seen with acetaminophen alone. Placebo was not effective for pain reduction.

"This is a first step towards the optimization of the management of acute low back pain. However, specific patient characteristics such as having allergies and comorbidities must always be taken into consideration," Baroncini said in a statement. "Further research will need to focus on the identification of the type of drugs that not only offer the best and quickest pain relief, but also show the lowest rate of symptom recurrence."

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We have limited data on the mechanisms of aspirin desensitization in patients with NSAID-induced urticaria/angioede… https://t.co/Z4VwZHm4e5December 30,2022

MONDAY, Nov. 21, 2022 (HealthDay News) -- Opioid initiation among patients with rheumatoid arthritis (RA) is associated with similar major adverse cardiovascular events (MACE) and all-cause mortality risk versus nonsteroidal anti-inflammatory drug (NSAID) initiation; however, opioids did contribute to a higher risk for venous thromboembolism, according to a study presented at the annual meeting of the American College of Rheumatology, held from Nov. 10 to 14 in Philadelphia.

Gulsen Ozen, M.D., from the University of Nebraska Medical Center in Bellevue, and colleagues assessed MACE risk with opioids versus NSAIDs in patients with RA. The analysis included matched cohorts of 4,778 opioid-initiating and 11,218 NSAID-initiating RA patients (1998 to 2021).

The researchers found that during the study period, there were 133 MACE in the opioid-initiating group versus 392 in the NSAID group (18.2 versus 14.6 per 1,000 person-years). Similarly, all-cause deaths were higher in the opioid group (95 deaths) versus the NSAID group (228 deaths; 12.6 versus 8.2 per 1,000 person-years). While incidence rates of MACE and all-cause mortality were lower among NSAID initiators than opioid initiators, the risk for MACE was similar in propensity-matched models (hazard ratio, 1.05, 95 percent confidence interval, 0.83 to 1.32), as was all-cause mortality (hazard ratio, 1.21; 95 percent confidence interval, 0.91 to 1.62). The risk for venous thromboembolism was significantly higher in opioid initiators than NSAID initiators (hazard ratio, 2.45; 95 percent confidence interval, 1.27 to 4.74).

"We hope our findings can decrease opioid prescriptions for pain in patients with inflammatory rheumatic diseases," Ozen said in a statement. "We have to remember that pain in inflammatory rheumatic diseases is multifactorial, and we should utilize nonpharmacological methods more often in this patient population."

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