Intravenous immunoglobulin G effectiveness evaluation for hemorrhagic cystitis treatment in allogeneic hematopoietic stem cell transplantation

Summary

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a frequent complication occurring in 11-31% of cases. HC can negatively influences early posttransplantation period, increases the duration and amount of blood transfusion therapy, leads to coagulation abnormalities, as well as to acute and chronic kidney damage and, as a consequence, reduces overall survival, increases the time of hospitalization and the costs of treatment. Currently, there are no available presented algorithms for the treatment with sufficient effectiveness. Aim of the present study was to evaluate the effectiveness of intravenous immunoglobulin G (IVIG) treatment for HC after allo-HSCT.

Patients and methods

From 2015 to 2018, 749 patients who underwent allo-HSCT in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation were enrolled into the retrospective analysis. HC developed in 10.8% (n=81) of the patients. The study included 49 patients with HC who received their first allo-HSCT and developed a late form of HC not earlier than D+6 after allo-HSCT; a group of patients receiving IVIG, only with early HC treatment performed not later than seven days after the HC onset. The standard accompanying therapy for the hemorrhagic cystitis therapy, such as enhanced infusion therapy, forced diuresis, non-steroidal anti-inflammatory drugs and spasmolytic drugs. Fourteen patients (28.6%) did not receive any specific treatment for HC. As for HC treatment, IVIG was administered in 71.4% (n=35) of the patients, at a dose of 0.4 g/kg once a day for 3-5 consecutive days. Both groups were comparable for age (7-54 years, median, 22 versus 3-54 years, median, 18, p=0.34), primary diagnosis (AML, 35.6% vs 40%; ALL, 50% vs 51.4%, p=0.77), type of transplantation (allo-HSCT, 60% vs 57.2%; haploidentical HSCT, 40% vs 42.8%, p=0.85), conditioning regimen (MAC, 71.2% and 60%; RIC, 28.8% and 40%, p=0.46), and the day of HC manifestation after HSCT (6 to 160 days, median – 41; 7-119 days, median, 38; p=0.75), respectively. HC treatment with IVIG was started 1-7 days after first HC signs, the median was 3 days.

The therapy efficiency was based on HC duration in the group of patients without specific therapy and HC duration from the beginning of IVIG therapy to the end of HC symptoms in group of patients who had received therapy. The criterion for HC completion was the last day of macrohematuria and microhematuria of less than 60 red blood cells per vision field in general urine testing.

Results

There were no statistically significant differences in the median HC duration between the IVIG recipient group (23 days) and patients, who did not receive specific treatment (17 days; p=0.37), as seen from Fig 1.

Figure 1. Comparative frequency of hemorrhagic cystitis in HSCT patients treated with or without IVIG

Conclusion

With a limited sample size of HSCT patients, we did not reveal any convincing therapeutic activity of IVIG when treating late hemorrhagic cystitis after allo-HSCT.

Keywords

Hematopoietic stem cell transplantation, hemorrhagic cystitis, IVIG.