nach oben

Erschienen in:

01.02.2020 | Original Article

Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation

verfasst von: Souichi Shiratori, Hiroyuki Ohigashi, Shuichiro Takahashi, Takahide Ara, Hideki Goto, Masao Nakagawa, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima, North Japan Hematology Study Group (NJHSG)

Erschienen in: Annals of Hematology | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Although a combination of calcineurin inhibitor and methotrexate (MTX) is used for graft-versus-host disease (GVHD) prophylaxis in umbilical cord blood transplantation (CBT), optimal dose of MTX for CBT remains to be determined.

We conducted a retrospective study to evaluate the safety and efficacy of standard-dose MTX (St-MTX, 15 mg/m² on day 1 and 10 mg/m² on days 3 and 6) and mini-dose MTX (Mini-MTX, 5 mg/m² on days 1, 3 and 6) for GVHD prophylaxis in patients who underwent single unit CBT against hematological malignancies.

Thirty-two and 26 patients received St-MTX and Mini-MTX, respectively. Cumulative incidence of neutrophil engraftment was significantly higher in the Mini-MTX group than in the St-MTX group (88.5% vs 65.6%, P = 0.00448). Cumulative incidences of grade II to IV and grade III to IV of acute graft-versus-host disease (GVHD) were 34.4% and 6.2% in the St-MTX group, and 34.6% and 7.7% in the Mini-MTX group with no statistical significance. One-year non-relapse mortality (NRM) was significantly lower in the Mini-MTX group compared to the St-MTX group (31.2% vs 3.8%, P = 0.00938), whereas relapse rate was not different between the groups. Multivariate analysis also indicated that Mini-MTX significantly improved engraftment (HR, 0.5359; 95% CI, 0.3082 to 0.9318; P = 0.0270) and reduced NRM (HR, 0.117; 95% CI, 0.0151 to 0.9067; P = 0.040).

Our study suggests that GVHD prophylaxis using Mini-MTX in CBT is feasible and associated with improvement of engraftment and reduction in NRM.

Nur mit Berechtigung zugänglich

Narimatsu H, Terakura S, Matsuo K et al (2007) Short-term methotrexate could reduce early immune reactions and improve outcomes in umbilical cord blood transplantation for adults. Bone Marrow Transplant 39:31–39CrossRef

Kato K, Yoshimi A, Ito E, Oki K, Hara J, Nagatoshi Y, Kikuchi A, Kobayashi R, Nagamura-Inoue T, Kai S, Azuma H, Takanashi M, Isoyama K, Kato S, Japan Cord Blood Bank Network (2011) Cord blood transplantation from unrelated donors for children with acute lymphoblastic leukemia in Japan: the impact of methotrexate on clinical outcomes. Biol Blood Marrow Transplant 17:1814–1821CrossRef

Terakura S, Wake A, Inamoto Y, Murata M, Sakai R, Yamaguchi T, Takahashi S, Uchida N, Onishi Y, Ohashi K, Ozawa Y, Kanamori H, Yamaguchi H, Fukuda T, Ichinohe T, Takanashi M, Atsuta Y, Teshima T (2017) Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil. Bone Marrow Transplant 52:423–430CrossRef

Terakura S, Kuwatsuka Y, Yamasaki S, Wake A, Kanda J, Inamoto Y, Mizuta S, Yamaguchi T, Uchida N, Kouzai Y, Aotsuka N, Ogawa H, Kanamori H, Nishiwaki K, Miyakoshi S, Onizuka M, Amano I, Fukuda T, Ichinohe T, Atsuta Y, Murata M, Teshima T (2017) GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia. Bone Marrow Transplant 52:1261–1267CrossRef

Kishi Y, Kami M, Miyakoshi S, Kanda Y, Murashige N, Teshima T, Kusumi E, Hara S, Matsumura T, Yuji K, Masuoka K, Wake A, Morinaga S, Kanemaru M, Hayashi T, Tanaka Y, Taniguchi S, Tokyo Stem Cell Transplant Consortium (2005) Early immune reaction after reduced-intensity cord-blood transplantation for adult patients. Transplantation 80:34–40CrossRef

O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, Raad II, Randolph AG, Rupp ME, Saint S, Healthcare Infection Control Practices Advisory Committee (HICPAC) (Appendix 1) (2011) Summary of recommendations: guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis 52:1087–1099CrossRef

Filipovich AH, Weisdorf D, Pavletic S et al (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. diagnosis and staging working group report. Biol Blood Marrow Transplant 11:945–956CrossRef

Sorror ML, Giralt S, Sandmaier BM, de Lima M, Shahjahan M, Maloney DG, Deeg HJ, Appelbaum FR, Storer B, Storb R (2007) Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 110:4606–4613CrossRef

Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, Maziarz RT, Antin JH, Soiffer RJ, Weisdorf DJ, Rizzo JD, Horowitz MM, Saber W (2014) Validation and refinement of the disease risk index for allogeneic stem cell transplantation. Blood 123:3664–3671CrossRef

10.

Kanda Y (2013) Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 48:452–458CrossRef

11.

Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J, Souillet G, Ferreira E, Laporte JP, Fernandez M, Chastang C (1997) Outcome of cord-blood transplantation from related and unrelated donors. Eurocord transplant group and the European blood and marrow transplantation group. N Engl J Med 337:373–381CrossRef

12.

Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR, Berkowitz RL, Cabbad M, Dobrila NL, Taylor PE, Rosenfield RE, Stevens CE (1998) Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 339:1565–1577CrossRef

13.

Yanada M, Konuma T, Kuwatsuka Y et al (2019) Unit selection for umbilical cord blood transplantation for adults with acute myeloid leukemia in complete remission: a Japanese experience. Bone Marrow Transplant

14.

Konuma T, Kato S, Oiwa-Monna M et al (2017) Cryopreserved CD34+ cell dose, but not Total nucleated cell dose, influences hematopoietic recovery and extensive chronic graft-versus-host disease after single-unit cord blood transplantation in adult patients. Biol Blood Marrow Transplant 23:1142–1150CrossRef

15.

Nakasone H, Tabuchi K, Uchida N, Ohno Y, Matsuhashi Y, Takahashi S, Onishi Y, Onizuka M, Kobayashi H, Fukuda T, Ichinohe T, Takanashi M, Kato K, Atsuta Y, Yabe H, Kanda Y (2019) Which is more important for the selection of cord blood units for haematopoietic cell transplantation: the number of CD34-positive cells or total nucleated cells? Br J Haematol 185:166–169CrossRef

16.

Ruggeri A, Sanz G, Bittencourt H, Sanz J, Rambaldi A, Volt F, Yakoub-Agha I, Ribera JM, Mannone L, Sierra J, Mohty M, Solano C, Nabhan S, Arcese W, Gluckman E, Labopin M, Rocha V, Eurocord and Acute Leukemia Working Party of European Blood and Marrow Transplant Group (2014) Comparison of outcomes after single or double cord blood transplantation in adults with acute leukemia using different types of myeloablative conditioning regimen, a retrospective study on behalf of Eurocord and the acute leukemia working party of EBMT. Leukemia 28:779–786CrossRef

17.

Nakasone H, Fuji S, Yakushijin K, Onizuka M, Shinohara A, Ohashi K, Miyamura K, Uchida N, Takanashi M, Ichinohe T, Atsuta Y, Fukuda T, Ogata M, Complication Working Group of Japanese Society for Hematopoietic Cell Transplantation (2017) Impact of total body irradiation on successful neutrophil engraftment in unrelated bone marrow or cord blood transplantation. Am J Hematol 92:171–178CrossRef

18.

Takanashi M, Atsuta Y, Fujiwara K et al (2010) The impact of anti-HLA antibodies on unrelated cord blood transplantations. Blood 116:2839–2846CrossRef

19.

Locatelli F, Rocha V, Reed W, Bernaudin F, Ertem M, Grafakos S, Brichard B, Li X, Nagler A, Giorgiani G, Haut PR, Brochstein JA, Nugent DJ, Blatt J, Woodard P, Kurtzberg J, Rubin CM, Miniero R, Lutz P, Raja T, Roberts I, Will AM, Yaniv I, Vermylen C, Tannoia N, Garnier F, Ionescu I, Walters MC, Lubin BH, Gluckman E, Eurocord Transplant Group (2003) Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood 101:2137–2143CrossRef

20.

Miyashita N, Endo T, Onozawa M et al (2017) Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 19:e12682CrossRef

21.

Inui Y, Yakushijin K, Okamura A et al (2019) Human herpesvirus 6 encephalitis in patients administered mycophenolate mofetil as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 21:e13024CrossRef

22.

Frangoul H, Wang L, Harrell FE Jr, Ho R, Domm J (2009) Preengraftment syndrome after unrelated cord blood transplant is a strong predictor of acute and chronic graft-versus-host disease. Biol Blood Marrow Transplant 15:1485–1488CrossRef

23.

Kanda J, Kaynar L, Kanda Y et al (2013) Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment. Bone Marrow Transplant 48:926–931CrossRef

24.

Isobe M, Konuma T, Kato S, Tanoue S, Mizusawa M, Oiwa-Monna M, Takahashi S, Tojo A (2019) Development of pre-engraftment syndrome, but not acute graft-versus-host disease, reduces relapse rate of acute Myelogenous leukemia after single cord blood transplantation. Biol Blood Marrow Transplant 25:1187–1196CrossRef

25.

Przepiorka D, Ippoliti C, Khouri I, Woo M, Mehra R, le Bherz D, Giralt S, Gajewski J, Fischer H, Fritsche H, Deisseroth AB, Cleary K, Champlin R, Besien K, Andersson B, Maher R, Fitzsimmons W (1996) Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after matched unrelated donor marrow transplantation. Blood 88:4383–4389CrossRef

26.

Uberti JP, Ayash L, Braun T, Reynolds C, Silver S, Ratanatharathorn V (2004) Tacrolimus as monotherapy or combined with minidose methotrexate for graft-versus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation: long-term outcomes. Bone Marrow Transplant 34:425–431CrossRef

27.

Saito B, Hattori N, Yamamoto K, Arai N, Kawaguchi Y, Fujiwara S, Kabasawa N, Tsukamoto H, Uto Y, Ariizumi H, Yanagisawa K, Nakamaki T (2016) Umbilical cord blood transplantation for adults using tacrolimus with two-day very-short-term methotrexate for graft-versus-host disease prophylaxis. Leuk Res 47:161–165CrossRef

28.

Adachi Y, Ozeki K, Ukai S, Sagou K, Fukushima N, Kohno A (2019) Optimal dosage of methotrexate for GVHD prophylaxis in umbilical cord blood transplantation. Int J Hematol 109:440–450CrossRef

29.

Yoshida S, Ohno Y, Nagafuji K et al (2019) Comparison of calcineurin inhibitors in combination with conventional methotrexate, reduced methotrexate, or mycophenolate mofetil for prophylaxis of graft-versus-host disease after umbilical cord blood transplantation. Ann Hematol 98:2579–2591CrossRef

30.

Fuji S, Tada Y, Nakata R, et al (2019) GVHD prophylaxis by tacrolimus and mini-MTX in single-unit CBT: a single institute experience. Int J Hematol

31.

Matsukawa T, Hashimoto D, Sugita J, Nakazawa S, Matsushita T, Kashiwazaki H, Goto H, Onozawa M, Kahata K, Fujimoto K, Endo T, Kondo T, Hashino S, Yamazaki Y, Teshima T (2016) Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD. Int J Hematol 104:117–124CrossRef

Titel: Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation
verfasst von: Souichi Shiratori
Hiroyuki Ohigashi
Shuichiro Takahashi
Takahide Ara
Hideki Goto
Masao Nakagawa
Junichi Sugita
Masahiro Onozawa
Kaoru Kahata
Tomoyuki Endo
Daigo Hashimoto
Takanori Teshima
North Japan Hematology Study Group (NJHSG)
Publikationsdatum: 01.02.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 3/2020
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-020-03937-3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2020

Poor prognosis in patients with diffuse large B cell lymphomas with bone marrow involvement possessing chromosomal abnormalities, despite aggressive treatment

Correction to: In the South African setting, HIV-associated Burkitt lymphoma is associated with frequent leukaemic presentation, complex cytogenetic karyotypes, and adverse clinical outcomes

Platelet counts of adults upon acute hospital admission to internal medicine units are a predictor of mortality

Impact of marrow blasts percentage on high-grade myelodysplastic syndrome assessed using revised international prognostic scoring system

Trametinib and Dabrafenib in histiocytic sarcoma transdifferentiated from chronic lymphocytic leukemia with a K-RAS and a unique BRAF mutation