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Colostrum and severe gut GVHD

September 1998
Bone Marrow Transplantation 22(4):402-3

DOI:10.1038/sj.bmt.1701369

Source
PubMed

Authors:

Taiiga Okamura

Tamagawa University

Keisei Kawa

Osaka Medical Center and Research Institute for Maternal and Child Health

…

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Correspondence

402

and non-aeruginosa Pseudomonas species: increasing inci-

dence of catheter-related infections. Medicine 1990; 69:

296–306.

6 Aoun M, van der Auwera P, Devleeshouwer C et al. Bactere-

mia caused by non-aeruginosa Pseudomonas species in a can-

cer center. J Hosp Infect 1994; 22: 307–316.

Colostrum and severe gut GVHD

Treatment of severe gut graft-versus-host disease (GVHD)

after allogeneic hematopoietic stem cell transplantation

(HSCT) remains problematic even though there have been

many advances in immunosuppressive therapy. Recently

we have treated nine patients who suffered from severe gut

GVHD: large volumes of watery and bloody stool, paralytic

ileus and severe abdominal pain. We gave them colostrum

for the treatment of severe gut GVHD and six out of nine

showed clinical improvement. A dose of colostrum was set

at 20 ml daily and given for 5 consecutive days. Colostrum

was obtained from random donors. Clinical data of these

nine patients are summarized in Table 1. Two of them

(UPN 151 and 157) were not evaluated because of poor

compliance. Rectal biopsies were performed in six cases

(UPN 147, 151, 159, 164, 166 and 173) and histological

ﬁndings were compatible with enteric GVHD in all cases.

Thrombotic microangiopathy combined with GVHD was

proven in UPN 151 and also CMV infection was conﬁrmed

by in situ hybridization in UPN 159. One typical case (UPN

147) is presented.

This patient was diagnosed with B-precursor ALL

(CD10 negative) when she was 3 months old and trans-

planted from an unrelated HLA-matched donor in second

complete remission when she was 1 year old. Conditioning

consisted of TBI (12 Gy), etoposide (60 mg/kg) and cyclo-

phosphamide (120 mg/kg). FK506 and methylprednisolone

Table 1 Summary of nine cases who underwent colostrum therapy for severe gut GVHD

UPN Age Disease Preconditioning SCT GVHD aGVHD Prior therapy of Immuno- Stage of gut GVHD Effectiveness

(years) regimen prophylaxis grade GVHD suppressive of colostrum

agent

pre- post-

administered

colostrum colostrum

with

colostrum

147 1 ALL TBI+VP16+Cy UBMT FK506+mPSL III Pulse, MTX, ATG, Pred VP16 4 0–1 +

151

1 JCML TBI+thioTEPA+LPAM RBMT CSA+mPSL III Pulse, Pred, MTX VP16 4 4 NE

157

16 ALL TBI+CA+LPAM UBMT FK506+mPSL III Pulse, mPSL — 4 4 NE

159

14 MDS TBI+thioTEPA+LPAM UBMT FK506+mPSL III Pulse, Pred MTX 4 3 +

162 4 ALL TBI+CA+LPAM CD34PBSCT FK506 III Pulse, Pred MTX 4 0–1 +

164 13 AML TBI+thioTEPA+LPAM UBMT FK506+mPSL III Pulse, mPSL MTX 4 4 −

166 13 AML TBI+LPAM UBMT FK506+mPSL III Pulse, Pred MTX 3 2 +

167 1 JCML TBI+thioTEPA+LPAM UBMT FK506+mPSL III Pulse, Pred, MTX — 3 1 +

173 6 ALL TBI+thioTEPA+LPAM UBMT FK506+mPSL III Pulse, Pred — 3 1 +

UBMT = HAL-matched BMT from unrelated donor; RBMT = HLA-matched BMT from related donor; CD34PBSCT = PBSCT using CD34-positive cells

from HLA haploidentical father; Pulse = high-dose methylprednisolone therapy (0.5 g/m

/day for 3 consecutive days); NE = not evaluable.

UPN151 and UPN157, Compliance of colostrum was poor because of nausea and vomiting. UPN151, histological ﬁnding of rectum was aGVHD

accompanied with thrombotic microangiopathy. UPN159, histological ﬁnding of rectum was compatible with aGVHD, and CMV infection was conﬁrmed

by in situ hybridization.

7 Musso D, Drancourt M, Bardot J, Legre R. Human infection

due to the CDC group IV c-2 bacterium: case report and

review. Clin Infect Dis 1994; 18: 482–484.

(mPSL) were used for GVHD prophylaxis. Ganciclovir was

administered from days −8to−1 because she was CMV-

seropositive. Engraftment was prompt. Neutrophils rose

to 0.5 × 10

/l on day 14. Platelets rose to 20 × 10

/l on

day 17. Reticulocytes reached 1% on day 57. Complete

chimerism was conﬁrmed by VNTR on day 47.

She developed grade III acute GVHD. A rash appeared

on day 15 followed by bloody diarrhea complicated by

paralytic ileus. The peak value of TB was 4.4 mg/dl on day

34. A rectal biopsy was performed and histological ﬁndings

were compatible with acute GVHD. CMV infection was

not detected by in situ hybridization. Symptoms of gut

GVHD persisted in spite of high-dose mPSL (pulse

therapy), methotrexate and anti-thymocyte globulin (ATG).

We therefore decided to use colostrum and low-dose etopo-

side (VP16) as a systemic immunosuppressive agent. Col-

ostrum obtained from random donors was administered

orally at 20 ml/day for 5 consecutive days. Her gut GVHD

disappeared soon after the colostrum therapy as shown in

Figure 1. In addition, the liver and skin GVHD improved.

It is well known that breast feeding plays an important

role for babies in preventing infection and in developing

the digestive system. Human milk, especially colostrum,

contains many materials such as cytokines (TGF

␤

, EGF,

etc) and sIgA.

The present trial is still preliminary and

the efﬁcacy of colostrum therapy for gut GVHD should be

conﬁrmed in more cases. In the same setting oral immuno-

globulin may be an alternative choice.

However, in our

Correspondence

403

BMT

FK506

Pulse

Pred

VP16

evacuation (times/day)

mPSL

MTX

ATG

Colostrum

bloody watery stool

020406080

rash

TB (mg/dl)

0 2040 6080

10 000

8000

6000

4000

2000

020406080

WBC (/ l)

Days after BMT

Figure 1 Clinical course of UPN 147.

limited experience colostrum seems to be superior. On the

basis of these ﬁndings we suggest a potential beneﬁt of

colostrum for severe gut GVHD.

M Inoue Department of Pediatrics, Osaka

T Okamura Medical Center and Research Institute

A Sawada for Maternal and Child Health, 840

K Kawa Murodo-cho, Izumu, Osaka 594–1101,

Japan

Myasthenia gravis post allogeneic bone

marrow transplantation revisited

We feel that it is appropriate to extend our previous report,

‘Myasthenia gravis in association with allogeneic bone

marrow transplant’,

in which we describe a 15-year-old

female with AML who underwent BMT in 1985. As we

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2 Kanfer EJ, Abrahamson G, Taylor J et al. Severe rotavirus-

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noted, her clinical course was complicated by the develop-

ment of chronic graft-versus-host disease as well as

generalized myasthenia gravis treated successfully with

corticosteroids, pyridostigmine and thymectomy.

In March 1997, 37 months after the initial diagnosis of

myasthenia gravis, the patient presented to a peripheral hos-

pital with progressive dysphagia, dysphonia, ptosis and

shoulder and pelvic girdle weakness. These symptoms

occurred while tapering prednisone to 5 mg/day. The

patient did not improve with prednisone 40 mg/day and

reinstitution of pyridostigmine. Despite hospitalization and

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Milk Diets Influence Doxorubicin-Induced Intestinal Toxicity in Piglets

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Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

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INT J HEMATOL

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Integrative Nutrition and Nutrition/Herbal Supplements

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Children with cancer frequently use complementary and alternative medicine (CAM), especially in conjunction with conventional therapy. Dietary supplements are a commonly used CAM modality, with the prevalence of supplement use ranging from 35% to 50% of children with cancer in surveys completed in the United States. Less is known about the use of dietary supplements in developing countries. The evidence for some dietary supplements providing some benefit to children with cancer is reviewed. Preliminary studies have shown that antioxidant status may affect chemotherapy tolerance in children with acute lymphoblastic leukemia. Other supplements, including TRAUMEEL S, glutamine, vitamin E, Immunocal, colostrum, and probiotics, may help to reduce gastrointestinal toxicities of chemotherapy and radiation. However, more definitive evidence is needed. Most dietary supplements have not been tested adequately to determine their safety and efficacy, with even less understood about their potential interactions with conventional chemotherapy and radiation. With the greater use of dietary supplements by patients with cancer, increasing scientific attention is being paid to the investigation of these therapies. But research on dietary supplements is complex and usually more difficult than that on conventional medications. Strong research designs are critical in obtaining information that will ultimately influence clinical practice and public awareness.

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Oct 1996
Res Comm Mol Pathol Pharmacol

Breast feeding improves the health of children. The greatest significance is to host defense, prevention of autoimmunity, and development of the digestive system; however, the underlying mechanisms for these effects are not well understood. Based on recent evidence that cytokines might be important in these processes, we have used ELISA to quantitate the cytokines in human colostrum, transitional, and mature milk from mothers delivering preterm or at term. We also used reverse transcription PCR to test breast milk cells for the production of cytokine mRNA. No significant (< 10 pg/ml) GM-CSF, SCF, LIF, MIP-1 alpha, IL-2, IL-4, IL-11, IL-12, IL-13, IL-15, sIL-2R, or IFN-gamma was detected. And, in contrast to earlier studies using bioassays or RIA, no significant IL-1 beta, TNF-alpha, or IL-6 was present; nor was IL-10, which had been tested using less specific antibodies. We did confirm the presence of high levels of M-CSF, which remained high throughout lactation. Human milk contained latent, but not free, TGF-beta 1, and especially TGF-beta 2, both of which may be activated by gastric acid pH. High levels of IL-1RA were detected, and like activated TGF-beta, may protect against autoimmunity. Chemokines, particularly GRO-alpha and MCP-1, but also RANTES and IL-8, were present and could protect against infection. Maternal cells in breast milk expressed mRNA for MCP-1 (20/20), IL-8 (14/20), TGF-beta 1 (14/16), TGF-beta 2 (4/6), M-CSF (9/12), IL-6 (6/12) and IL-1 beta (7/12), and may be a source of these cytokines. mRNA for IL-2, IL-10, IFN-gamma, TNF-alpha was not detected and only weak expression was found for RANTES (1/18). There was considerable variability between individual women, and women delivering preterm had lower levels of several cytokines in colostrum than women delivering at term. Yet, cytokine levels remained high months to years into lactation, providing immunological benefit to the breastfed infant/child.

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